544 results on '"Gómez-Skarmeta, José Luis"'
Search Results
2. Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci
- Author
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D’haene, Eva, López-Soriano, Víctor, Martínez-García, Pedro Manuel, Kalayanamontri, Soraya, Rey, Alfredo Dueñas, Sousa-Ortega, Ana, Naranjo, Silvia, Van de Sompele, Stijn, Vantomme, Lies, Mahieu, Quinten, Vergult, Sarah, Neto, Ana, Gómez-Skarmeta, José Luis, Martínez-Morales, Juan Ramón, Bauwens, Miriam, Tena, Juan Jesús, and De Baere, Elfride
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- 2024
- Full Text
- View/download PDF
3. The little skate genome and the evolutionary emergence of wing-like fins
- Author
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Marlétaz, Ferdinand, de la Calle-Mustienes, Elisa, Acemel, Rafael D, Paliou, Christina, Naranjo, Silvia, Martínez-García, Pedro Manuel, Cases, Ildefonso, Sleight, Victoria A, Hirschberger, Christine, Marcet-Houben, Marina, Navon, Dina, Andrescavage, Ali, Skvortsova, Ksenia, Duckett, Paul Edward, González-Rajal, Álvaro, Bogdanovic, Ozren, Gibcus, Johan H, Yang, Liyan, Gallardo-Fuentes, Lourdes, Sospedra, Ismael, Lopez-Rios, Javier, Darbellay, Fabrice, Visel, Axel, Dekker, Job, Shubin, Neil, Gabaldón, Toni, Nakamura, Tetsuya, Tena, Juan J, Lupiáñez, Darío G, Rokhsar, Daniel S, and Gómez-Skarmeta, José Luis
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Human Genome ,Generic health relevance ,Animals ,Animal Fins ,Genomics ,Homeodomain Proteins ,Skates ,Fish ,Zebrafish ,Biological Evolution ,Genome ,Genes ,Reporter ,General Science & Technology - Abstract
Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.
- Published
- 2023
4. The little skate genome and the evolutionary emergence of wing-like fin appendages
- Author
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Marlétaz, Ferdinand, de la Calle-Mustienes, Elisa, Acemel, Rafael D, Nakamura, Tetsuya, Paliou, Christina, Naranjo, Silvia, Martínez-García, Pedro Manuel, Cases, Ildefonso, Sleight, Victoria A, Hirschberger, Christine, Marcet-Houben, Marina, Navon, Dina, Andrescavage, Ali, Skvortsova, Ksenia, Duckett, Paul Edward, González-Rajal, Álvaro, Bogdanovic, Ozren, Gibcus, Johan H, Yang, Liyan, Gallardo-Fuentes, Lourdes, Sospedra, Ismael, Lopez-Rios, Javier, Darbellay, Fabrice, Visel, Axel, Dekker, Job, Shubin, Neil, Gabaldón, Toni, Tena, Juan J, Lupiáñez, Darío G, Rokhsar, Daniel S, and Gómez-Skarmeta, José Luis
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Generic health relevance - Abstract
Skates are cartilaginous fish whose novel body plan features remarkably enlarged wing-like pectoral fins that allow them to thrive in benthic environments. The molecular underpinnings of this unique trait, however, remain elusive. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins (gene expression, chromatin occupancy and three-dimensional (3D) conformation) we find skate-specific genomic rearrangements that alter the 3D regulatory landscape of genes involved in the planar cell polarity (PCP) pathway. Functional inhibition of PCP signaling resulted in marked reduction of anterior fin size, confirming this pathway as a major contributor of batoid fin morphology. We also identified a fin-specific enhancer that interacts with 3' HOX genes, consistent with the redeployment of Hox gene expression in anterior pectoral fins, and confirmed the potential of this element to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganizations and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.
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- 2022
5. 3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- Author
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Hoencamp, Claire, Dudchenko, Olga, Elbatsh, Ahmed MO, Brahmachari, Sumitabha, Raaijmakers, Jonne A, van Schaik, Tom, Sedeño Cacciatore, Ángela, Contessoto, Vinícius G, van Heesbeen, Roy GHP, van den Broek, Bram, Mhaskar, Aditya N, Teunissen, Hans, St Hilaire, Brian Glenn, Weisz, David, Omer, Arina D, Pham, Melanie, Colaric, Zane, Yang, Zhenzhen, Rao, Suhas SP, Mitra, Namita, Lui, Christopher, Yao, Weijie, Khan, Ruqayya, Moroz, Leonid L, Kohn, Andrea, St Leger, Judy, Mena, Alexandria, Holcroft, Karen, Gambetta, Maria Cristina, Lim, Fabian, Farley, Emma, Stein, Nils, Haddad, Alexander, Chauss, Daniel, Mutlu, Ayse Sena, Wang, Meng C, Young, Neil D, Hildebrandt, Evin, Cheng, Hans H, Knight, Christopher J, Burnham, Theresa LU, Hovel, Kevin A, Beel, Andrew J, Mattei, Pierre-Jean, Kornberg, Roger D, Warren, Wesley C, Cary, Gregory, Gómez-Skarmeta, José Luis, Hinman, Veronica, Lindblad-Toh, Kerstin, Di Palma, Federica, Maeshima, Kazuhiro, Multani, Asha S, Pathak, Sen, Nel-Themaat, Liesl, Behringer, Richard R, Kaur, Parwinder, Medema, René H, van Steensel, Bas, de Wit, Elzo, Onuchic, José N, Di Pierro, Michele, Lieberman Aiden, Erez, and Rowland, Benjamin D
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Human Genome ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Adenosine Triphosphatases ,Algorithms ,Animals ,Biological Evolution ,Cell Nucleolus ,Cell Nucleus ,Centromere ,Chromosomes ,Chromosomes ,Human ,DNA-Binding Proteins ,Eukaryota ,Genome ,Genome ,Human ,Genomics ,Heterochromatin ,Humans ,Interphase ,Mitosis ,Models ,Biological ,Multiprotein Complexes ,Telomere ,General Science & Technology - Abstract
We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
- Published
- 2021
6. The emergence of the brain non-CpG methylation system in vertebrates
- Author
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de Mendoza, Alex, Poppe, Daniel, Buckberry, Sam, Pflueger, Jahnvi, Albertin, Caroline B, Daish, Tasman, Bertrand, Stephanie, de la Calle-Mustienes, Elisa, Gómez-Skarmeta, José Luis, Nery, Joseph R, Ecker, Joseph R, Baer, Boris, Ragsdale, Clifton W, Grützner, Frank, Escriva, Hector, Venkatesh, Byrappa, Bogdanovic, Ozren, and Lister, Ryan
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Biological Sciences ,Genetics ,Human Genome ,Pediatric ,Neurodegenerative ,Brain Disorders ,Neurosciences ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Brain ,DNA Methylation ,Genome ,Methyl-CpG-Binding Protein 2 ,Vertebrates ,Ecology ,Evolutionary biology ,Environmental management - Abstract
Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.
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- 2021
7. Ptychodera flava genomics and transcriptomics data
- Author
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Ministerio de Ciencia e Innovación (España), Tena, Juan J. [0000-0001-8165-7984], Gómez-Skarmeta, José Luis [0000-0001-5125-4332], Pérez-Posada, Alberto, Lin, Che-Yi, Fan, Tzu-Pei, Lin, Ching-Yi, Chen, Yi-Chih, Gómez-Skarmeta, José Luis, Yu, Jr-Kai, Su, Yi-Hsien, Tena, Juan J., Ministerio de Ciencia e Innovación (España), Tena, Juan J. [0000-0001-8165-7984], Gómez-Skarmeta, José Luis [0000-0001-5125-4332], Pérez-Posada, Alberto, Lin, Che-Yi, Fan, Tzu-Pei, Lin, Ching-Yi, Chen, Yi-Chih, Gómez-Skarmeta, José Luis, Yu, Jr-Kai, Su, Yi-Hsien, and Tena, Juan J.
- Abstract
Analysis of the transcriptomes and chromatin accessibility of multiple developmental stages of the indirect-developing hemichordate Ptychodera flava. After the individual analysis of each sample, integration of ATACseq and RNAseq data was performed in order to reconstruct genetic and regulatory networks. These data were also compared to other species, what could shed light on deuterostome evolution.
- Published
- 2024
8. The Shh/Gli3 gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits
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Letelier, Joaquín, Naranjo, Silvia, Sospedra-Arrufat, Ismael, Martinez-Morales, Juan Ramón, Lopez-Rios, Javier, Shubin, Neil, and Gómez-Skarmeta, José Luis
- Published
- 2021
9. Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements
- Author
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Baranasic, Damir, Hörtenhuber, Matthias, Balwierz, Piotr J., Zehnder, Tobias, Mukarram, Abdul Kadir, Nepal, Chirag, Várnai, Csilla, Hadzhiev, Yavor, Jimenez-Gonzalez, Ada, Li, Nan, Wragg, Joseph, D’Orazio, Fabio M., Relic, Dorde, Pachkov, Mikhail, Díaz, Noelia, Hernández-Rodríguez, Benjamín, Chen, Zelin, Stoiber, Marcus, Dong, Michaël, Stevens, Irene, Ross, Samuel E., Eagle, Anne, Martin, Ryan, Obasaju, Oluwapelumi, Rastegar, Sepand, McGarvey, Alison C., Kopp, Wolfgang, Chambers, Emily, Wang, Dennis, Kim, Hyejeong R., Acemel, Rafael D., Naranjo, Silvia, Łapiński, Maciej, Chong, Vanessa, Mathavan, Sinnakaruppan, Peers, Bernard, Sauka-Spengler, Tatjana, Vingron, Martin, Carninci, Piero, Ohler, Uwe, Lacadie, Scott Allen, Burgess, Shawn M., Winata, Cecilia, van Eeden, Freek, Vaquerizas, Juan M., Gómez-Skarmeta, José Luis, Onichtchouk, Daria, Brown, Ben James, Bogdanovic, Ozren, van Nimwegen, Erik, Westerfield, Monte, Wardle, Fiona C., Daub, Carsten O., Lenhard, Boris, and Müller, Ferenc
- Published
- 2022
- Full Text
- View/download PDF
10. Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.
- Author
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Lin, Che-Yi, Marlétaz, Ferdinand, Pérez-Posada, Alberto, Martínez-García, Pedro Manuel, Schloissnig, Siegfried, Peluso, Paul, Conception, Greg T., Bump, Paul, Chen, Yi-Chih, Chou, Cindy, Lin, Ching-Yi, Fan, Tzu-Pei, Tsai, Chang-Tai, Gómez Skarmeta, José Luis, Tena, Juan J., Lowe, Christopher J., Rank, David R., Rokhsar, Daniel S., Yu Jr, Kai, and Su, Yi-Hsien
- Subjects
CHROMOSOMES ,CHROMOSOMAL rearrangement ,GENOMES ,SEA urchins ,COMPARATIVE method ,HOMEOBOX genes ,COMPARATIVE genomics - Abstract
Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to understand their diversification. This study uses chromosome-level genome assemblies of two hemichordates to help infer the genomic architecture of the deuterostome common ancestor and subsequent lineage-specific rearrangement events. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
- Author
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García-Pérez, Raquel, Esteller-Cucala, Paula, Mas, Glòria, Lobón, Irene, Di Carlo, Valerio, Riera, Meritxell, Kuhlwilm, Martin, Navarro, Arcadi, Blancher, Antoine, Di Croce, Luciano, Gómez-Skarmeta, José Luis, Juan, David, and Marquès-Bonet, Tomàs
- Published
- 2021
- Full Text
- View/download PDF
12. Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci.
- Author
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D'haene, Eva, López-Soriano, Víctor, Martínez-García, Pedro Manuel, Kalayanamontri, Soraya, Rey, Alfredo Dueñas, Sousa-Ortega, Ana, Naranjo, Silvia, Van de Sompele, Stijn, Vantomme, Lies, Mahieu, Quinten, Vergult, Sarah, Neto, Ana, Gómez-Skarmeta, José Luis, Martínez-Morales, Juan Ramón, Bauwens, Miriam, Tena, Juan Jesús, and De Baere, Elfride
- Published
- 2024
- Full Text
- View/download PDF
13. Evolutionary emergence of the rac3b/rfng/sgca regulatory cluster refined mechanisms for hindbrain boundaries formation
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Letelier, Joaquín, Terriente, Javier, Belzunce, Ivan, Voltes, Adria, Undurraga, Cristian Alberto, Polvillo, Rocio, Devos, Lucie, Tena, Juan J., Maeso, Ignacio, Retaux, Sylvie, Gomez-Skarmeta, José Luis, Martínez-Morales, Juan R., and Pujades, Cristina
- Published
- 2018
14. Comparative 3D genome analysis between neural retina and RPE reveals differentialcis-regulatory interactions at retinal disease loci
- Author
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D’haene, Eva, primary, Soriano, Victor López, additional, Martínez-García, Pedro Manuel, additional, Kalayanamontri, Soraya, additional, Dueñas Rey, Alfredo, additional, Sousa-Ortega, Ana, additional, Naranjo, Silvia, additional, Van de Sompele, Stijn, additional, Vantomme, Lies, additional, Mahieu, Quinten, additional, Vergult, Sarah, additional, Neto, Ana Bastos, additional, Gómez-Skarmeta, José Luis, additional, Martínez-Morales, Juan R., additional, Bauwens, Miriam, additional, Tena, Juan J., additional, and De Baere, Elfride, additional
- Published
- 2023
- Full Text
- View/download PDF
15. A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
- Author
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Letelier, Joaquín, de la Calle-Mustienes, Elisa, Pieretti, Joyce, Naranjo, Silvia, Maeso, Ignacio, Nakamura, Tetsuya, Pascual-Anaya, Juan, Shubin, Neil H., Schneider, Igor, Martinez-Morales, Juan Ramón, and Gómez-Skarmeta, José Luis
- Published
- 2018
- Full Text
- View/download PDF
16. The little skate genome and the evolutionary emergence of wing-like fins
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Rutgers University, National Science Foundation (US), National Institutes of Health (US), Okinawa Institute of Science and Technology, German Research Foundation, Helmholtz Association, EMBO, Junta de Andalucía, European Research Council, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Royal Society (UK), Wolfson Foundation, Ministerio de Ciencia e Innovación (España), Marlétaz, Ferdinand, Calle-Mustienes, Elisa de la, Acemel, Rafael D., Paliou, Christina, Naranjo, Silvia, Martínez-García, Pedro Manuel, Cases, Ildefonso, Sleight, Victoria A., Hirschberger, Christine, Marcet-Houben, Marina, Navon, Dina, Andrescavage, Ali, Skvortsova, Ksenia, Duckett, Paul Edward, González-Rajal, Álvaro, Bogdanovic, Ozren, Gibcus, Johan H., Yang, Liyan, Gallardo-Fuentes, Lourdes, Sospedra, Ismael, López-Ríos, Javier, Darbellay, Fabrice, Visel, Axel, Dekker, Job, Shubin, Neil H., Gabaldón, Toni, Nakamura, Tetsuya, Tena, Juan J., Lupiáñez, Darío G., Rokhsar, Daniel S., Gómez-Skarmeta, José Luis, Rutgers University, National Science Foundation (US), National Institutes of Health (US), Okinawa Institute of Science and Technology, German Research Foundation, Helmholtz Association, EMBO, Junta de Andalucía, European Research Council, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Royal Society (UK), Wolfson Foundation, Ministerio de Ciencia e Innovación (España), Marlétaz, Ferdinand, Calle-Mustienes, Elisa de la, Acemel, Rafael D., Paliou, Christina, Naranjo, Silvia, Martínez-García, Pedro Manuel, Cases, Ildefonso, Sleight, Victoria A., Hirschberger, Christine, Marcet-Houben, Marina, Navon, Dina, Andrescavage, Ali, Skvortsova, Ksenia, Duckett, Paul Edward, González-Rajal, Álvaro, Bogdanovic, Ozren, Gibcus, Johan H., Yang, Liyan, Gallardo-Fuentes, Lourdes, Sospedra, Ismael, López-Ríos, Javier, Darbellay, Fabrice, Visel, Axel, Dekker, Job, Shubin, Neil H., Gabaldón, Toni, Nakamura, Tetsuya, Tena, Juan J., Lupiáñez, Darío G., Rokhsar, Daniel S., and Gómez-Skarmeta, José Luis
- Abstract
Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins—including gene expression, chromatin occupancy and three-dimensional conformation—we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.
- Published
- 2023
17. Partial functional divergence of the paralog genes znf503 and znf703 during zebrafish embryonic development
- Author
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Moreno Oñate, Marta, Gómez-Skarmeta, José Luis, Tena, Juan J., Franke, Martin, Moreno Oñate, Marta, Gómez-Skarmeta, José Luis, Tena, Juan J., and Franke, Martin
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- 2023
18. MIR retrotransposon sequences provide insulators to the human genome
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Wang, Jianrong, Vicente-García, Cristina, Seruggia, Davide, Moltó, Eduardo, Fernandez-Miñán, Ana, Neto, Ana, Lee, Elbert, Gómez-Skarmeta, José Luis, Montoliu, Lluís, Lunyak, Victoria V., and Jordan, I. King
- Published
- 2015
19. Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders
- Author
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Gómez-Marín, Carlos, Tena, Juan J., Acemel, Rafael D., López-Mayorga, Macarena, Naranjo, Silvia, de la Calle-Mustienes, Elisa, Maeso, Ignacio, Beccari, Leonardo, Aneas, Ivy, Vielmas, Erika, Bovolenta, Paola, Nobrega, Marcelo A., Carvajal, Jaime, and Gómez-Skarmeta, José Luis
- Published
- 2015
20. Deep conservation of wrist and digit enhancers in fish
- Author
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Gehrke, Andrew R., Schneider, Igor, de la Calle-Mustienes, Elisa, Tena, Juan J., Gomez-Marin, Carlos, Chandran, Mayuri, Nakamura, Tetsuya, Braasch, Ingo, Postlethwait, John H., Gómez-Skarmeta, José Luis, and Shubin, Neil H.
- Published
- 2015
21. Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy
- Author
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Van de Sompele, Stijn, Small, Kent W., Cicekdal, Munevver Burcu, Soriano, Víctor López, D’haene, Eva, Shaya, Fadi S., Agemy, Steven, Van der Snickt, Thijs, Rey, Alfredo Dueñas, Rosseel, Toon, Van Heetvelde, Mattias, Vergult, Sarah, Balikova, Irina, Bergen, Arthur A., Boon, Camiel J.F., De Zaeytijd, Julie, Inglehearn, Chris F., Kousal, Bohdan, Leroy, Bart P., Rivolta, Carlo, Vaclavik, Veronika, van den Ende, Jenneke, van Schooneveld, Mary J., Gómez-Skarmeta, José Luis, Tena, Juan J., Martinez-Morales, Juan R., Liskova, Petra, Vleminckx, Kris, De Baere, Elfride, Human Genetics, ANS - Complex Trait Genetics, ARD - Amsterdam Reproduction and Development, Ophthalmology, Ghent University, European Commission, Foundation Fighting Blindness, and Research Foundation - Flanders
- Subjects
Adult ,EXPRESSION ,DOMAINS ,PHOTORECEPTOR ,North Carolina macular dystrophy, NCMD ,non-coding single-nucleotide variants, SNVs ,PRDM13 ,Retina ,STRUCTURAL VARIANTS ,Xenopus laevis ,Genetics ,Medicine and Health Sciences ,Animals ,Humans ,Ccis-regulatory elements, CREswhole-genome sequencing ,North Carolina macular dystrophy ,Genetics (clinical) ,Corneal Dystrophies, Hereditary ,NCMD ,enhanceropathy ,Biology and Life Sciences ,TRANSGENESIS ,multi-omics ,GENE ,DUPLICATION ,UMI-4 ,Pedigree ,FAMILY ,GENOME ,cis-regulatory elements, CREs ,whole-genome sequencing ,cis-regulatory elements ,UMI-4C ,CREs ,non-coding single-nucleotide variants ,SNVs ,Human medicine ,human retina ,Tomography, Optical Coherence ,IRX1 - Abstract
North Carolina macular dystrophy (NCMD) is a rare autosomal-dominant disease affecting macular development. The disease is caused by non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications in two distinct chromosomal loci, overlapping DNase I hypersensitive sites near either PRDM13 or IRX1. To unravel the mechanisms by which these variants cause disease, we first established a genome-wide multi-omics retinal database, RegRet. Integration of UMI-4C profiles we generated on adult human retina then allowed fine-mapping of the interactions of the PRDM13 and IRX1 promoters and the identification of eighteen candidate cis-regulatory elements (cCREs), the activity of which was investigated by luciferase and Xenopus enhancer assays. Next, luciferase assays showed that the non-coding SNVs located in the two hotspot regions of PRDM13 affect cCRE activity, including two NCMD-associated non-coding SNVs that we identified herein. Interestingly, the cCRE containing one of these SNVs was shown to interact with the PRDM13 promoter, demonstrated in vivo activity in Xenopus, and is active at the developmental stage when progenitor cells of the central retina exit mitosis, suggesting that this region is a PRDM13 enhancer. Finally, mining of single-cell transcriptional data of embryonic and adult retina revealed the highest expression of PRDM13 and IRX1 when amacrine cells start to synapse with retinal ganglion cells, supporting the hypothesis that altered PRDM13 or IRX1 expression impairs interactions between these cells during retinogenesis. Overall, this study provides insight into the cis-regulatory mechanisms of NCMD and supports that this condition is a retinal enhanceropathy., This work was supported by grants from Ghent University Special Research Fund (BOF20/GOA/023) (E.D.B., K.V., B.P.L.); Ghent University Hospital Innovation Fund NucleUZ (E.D.B.); JED Foundation (E.D.B.); H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN) StarT (grant No. 813490) (E.D.B., K.V., J.L.G.-S., J.J.T., J.R.M.-M.); EJP RD Solve-RET EJPRD19-234 (E.D.B., P.L.,B.K., C.R., J.L.G.-S., J.J.T., J.R.M.-M.), SNSF grant # 204285 (C.R.), and Foundation Fighting Blindness in Columbia, MD (grant #: BR-GE-1216-0715-CSH). S.V.d.S. (1145719N) is PhD fellow of the Research Foundation Flanders (FWO), E.D.B. (1802220N) and B.P.L. (1803816N) are FWO Senior Clinical Investigators; M.B.C., V.L.S., and A.D.R. are Early Starting Researcher of ITN StarT (grant # 813490). B.K., B.P.L., C.J.F.B., E.D.B., P.L., and V.V. are members of ERN-EYE (Framework Partnership Agreement No 739534-ERNEYE). K.W.S. received an unrestricted grant from The Molecular Insight Research Foundation.
- Published
- 2022
22. Impact of signaling pathways in the cis-regulation during embryonic development
- Author
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Moreno Oñate, Marta, Jiménez-Gancedo, Sandra, Gómez-Skarmeta, José Luis, and Tena, Juan J.
- Abstract
Trabajo presentado en el 19th International Congress of Developmental Biology, celebrado en Guia (Portugal) del 16 al 20 de octubre de 2022., The animal body plan formation takes place during the embryonic development and it results from the precise spatio-temporal regulation of the gene expression. The animal form evolves largely by altering the expression of functionally conserved developmental genes and the vast networks they control. Most of the genomic signatures underlying key evolutionary processes can be found in the cis-regulatory elements (CREs) that control when, where and how much the genes are transcribed. We have identified genome-wide CREs acting during early development in zebrafish at different embryonic stages. To do that, we performed both ATAC-seq and RNA-seq, which allowed us to link the identified CREs to their target developmental genes and determine how their activity change in the different developmental stages. Several works over the last decades have shown that regulatory DNA can act at long distances, often more than 1 Mb, allowing the contact with promoters of target genes through chromatin loops. These enhancer-promoter physical interactions occur in a highly regulated manner, showing the importance of a precise regulation of the gene expression along development and animal evolution. To identify activated or repressed enhancers upon modulation of the genetic pathways, embryos have been treated with different drugs during the gastrulation period, when body plan basic layout is generated. At this point the open chromatin profiling have been done at three different stages: 80% of epiboly (gastrulation), 12 somites (neurulation) and 24hpf stage (organogenesis). Altogether, the goal of this project is to understand how developmental signaling pathways control CREs activity and regulate gene expression over different stages during the embryonic development.
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- 2022
23. Deep conservation of cis-regulatory elements in metazoans
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Maeso, Ignacio, Irimia, Manuel, Tena, Juan J., Casares, Fernando, and Gómez-Skarmeta, José Luis
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- 2013
- Full Text
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24. Regulatory Architecture of the RCA Gene Cluster Captures an Intragenic TAD Boundary, CTCF-Mediated Chromatin Looping and a Long-Range Intergenic Enhancer
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Cheng, Jessica, primary, Clayton, Joshua S., additional, Acemel, Rafael D., additional, Zheng, Ye, additional, Taylor, Rhonda L., additional, Keleş, Sündüz, additional, Franke, Martin, additional, Boackle, Susan A., additional, Harley, John B., additional, Quail, Elizabeth, additional, Gómez-Skarmeta, José Luis, additional, and Ulgiati, Daniela, additional
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- 2022
- Full Text
- View/download PDF
25. Insights into deuterostome evolution from the biphasic transcriptional programme of hemichordates
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Perez-Posada, Alberto, primary, Lin, Che-Yi, additional, Fan, Tzu-Pei, additional, Lin, Ching-Yi, additional, Chen, Yi-Chih, additional, Gómez Skarmeta, José Luis, additional, Yu, Jr-Kai, additional, Su, Yi-Hsien, additional, and Tena, Juan J., additional
- Published
- 2022
- Full Text
- View/download PDF
26. MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines
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Corujo, David, primary, Malinverni, Roberto, additional, Carrillo-Reixach, Juan, additional, Meers, Oliver, additional, Garcia-Jaraquemada, Arce, additional, Le Pannérer, Marguerite-Marie, additional, Valero, Vanesa, additional, Pérez, Ainhoa, additional, Del Río-Álvarez, Álvaro, additional, Royo, Laura, additional, Pérez-González, Beatriz, additional, Raurell, Helena, additional, Acemel, Rafael D., additional, Santos-Pereira, José M., additional, Garrido-Pontnou, Marta, additional, Gómez-Skarmeta, José Luis, additional, Pasquali, Lorenzo, additional, Manyé, Josep, additional, Armengol, Carolina, additional, and Buschbeck, Marcus, additional
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- 2022
- Full Text
- View/download PDF
27. Early evolution of the T-box transcription factor family
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Sebé-Pedrós, Arnau, Ariza-Cosanoc, Ana, Weirauch, Matthew T., Leininger, Sven, Yang, Ally, Torruella, Guifré, Adamski, Marcin, Adamska, Maja, Hughes, Timothy R., Gómez-Skarmeta, José Luis, and Ruiz-Trillo, Iñaki
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- 2013
28. Parallel evolution of amphioxus and vertebrate small-scale gene duplications
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Swiss National Science Foundation, Royal Society (UK), European Research Council, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Brasó-Vives, Marina, Marlétaz, Ferdinand, Echchiki, Amina, Mantica, Federica, Acemel, Rafael D., Gómez-Skarmeta, José Luis, Hartasánchez, Diego A., Targa, Lorlane Le, Pontarotti, Pierre, Tena, Juan J., Maeso, Ignacio, Escrivá, Héctor, Irimia, Manuel, Robinson-Rechavi, Marc, Swiss National Science Foundation, Royal Society (UK), European Research Council, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Brasó-Vives, Marina, Marlétaz, Ferdinand, Echchiki, Amina, Mantica, Federica, Acemel, Rafael D., Gómez-Skarmeta, José Luis, Hartasánchez, Diego A., Targa, Lorlane Le, Pontarotti, Pierre, Tena, Juan J., Maeso, Ignacio, Escrivá, Héctor, Irimia, Manuel, and Robinson-Rechavi, Marc
- Abstract
[Background]: Amphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Small-scale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R whole-genome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates. [Results]: We present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We find that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We find parallel gene duplication profiles between amphioxus and vertebrates and conserved functional constraints in gene duplication. Moreover, amphioxus gene duplicates show levels of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also find strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. floridae, with two major chromosomal rearrangements. [Conclusions]: In contrast to their slower molecular and morphological evolution, amphioxus’ small-scale gene duplication history resembles that of the vertebrate lineage both in quantitative and in functional terms.
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- 2022
29. Active DNA demethylation of developmental cis-regulatory regions predates vertebrate origins
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Australian Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Skvortsova, Ksenia, Bertrand, Stephanie, Voronov, D., Duckett, Paul Edward, Ross, Samuel E., Magri, Marta Silvia, Maeso, Ignacio, Weatheritt, Robert J., Gómez-Skarmeta, José Luis, Ina Arnone, María, Escrivá, Héctor, Bogdanovic, Ozren, Australian Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Skvortsova, Ksenia, Bertrand, Stephanie, Voronov, D., Duckett, Paul Edward, Ross, Samuel E., Magri, Marta Silvia, Maeso, Ignacio, Weatheritt, Robert J., Gómez-Skarmeta, José Luis, Ina Arnone, María, Escrivá, Héctor, and Bogdanovic, Ozren
- Abstract
DNA methylation [5-methylcytosine (5mC)] is a repressive gene-regulatory mark required for vertebrate embryogenesis. Genomic 5mC is tightly regulated through the action of DNA methyltransferases, which deposit 5mC, and ten-eleven translocation (TET) enzymes, which participate in its active removal through the formation of 5-hydroxymethylcytosine (5hmC). TET enzymes are essential for mammalian gastrulation and activation of vertebrate developmental enhancers; however, to date, a clear picture of 5hmC function, abundance, and genomic distribution in nonvertebrate lineages is lacking. By using base-resolution 5mC and 5hmC quantification during sea urchin and lancelet embryogenesis, we shed light on the roles of nonvertebrate 5hmC and TET enzymes. We find that these invertebrate deuterostomes use TET enzymes for targeted demethylation of regulatory regions associated with developmental genes and show that the complement of identified 5hmC-regulated genes is conserved to vertebrates. This work demonstrates that active 5mC removal from regulatory regions is a common feature of deuterostome embryogenesis suggestive of an unexpected deep conservation of a major gene-regulatory module.
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- 2022
30. Gene regulatory networks of epidermal and neural fate choice in a chordate
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Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), European Commission, Institut Universitaire de France, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Leon, Anthony, Subirana, Lucie, Magre, Kevin, Cases, Ildefonso, Tena, Juan J., Irimia, Manuel, Gómez-Skarmeta, José Luis, Escrivá, Héctor, Bertrand, Stephanie, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), European Commission, Institut Universitaire de France, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Leon, Anthony, Subirana, Lucie, Magre, Kevin, Cases, Ildefonso, Tena, Juan J., Irimia, Manuel, Gómez-Skarmeta, José Luis, Escrivá, Héctor, and Bertrand, Stephanie
- Abstract
Neurons are a highly specialized cell type only found in metazoans. They can be scattered throughout the body or grouped together, forming ganglia or nerve cords. During embryogenesis, centralized nervous systems develop from the ectoderm, which also forms the epidermis. How pluripotent ectodermal cells are directed toward neural or epidermal fates, and to which extent this process is shared among different animal lineages, are still open questions. Here, by using micromere explants, we were able to define in silico the putative gene regulatory networks (GRNs) underlying the first steps of the epidermis and the central nervous system formation in the cephalochordate amphioxus. We propose that although the signal triggering neural induction in amphioxus (i.e., Nodal) is different from vertebrates, the main transcription factors implicated in this process are conserved. Moreover, our data reveal that transcription factors of the neural program seem to not only activate neural genes but also to potentially have direct inputs into the epidermal GRN, suggesting that the Nodal signal might also contribute to neural fate commitment by repressing the epidermal program. Our functional data on whole embryos support this result and highlight the complex interactions among the transcription factors activated by the signaling pathways that drive ectodermal cell fate choice in chordates.
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- 2022
31. Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy
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Ghent University, European Commission, Foundation Fighting Blindness, Research Foundation - Flanders, Sompele, Stijn Van de, Small, Kent W., Burcu Cicekdal, Munevver, López Soriano, Víctor, D’haene, Eva, Shaya, Fadi S., Agemy, Steven, Snickt, Thijs Van der, Dueñas Rey, Alfredo, Rosseel, Toon, Heetvelde, Mattias Van, Vergult, Sarah, Balikova, Irina, Bergen, Arthur A., Boon, Camiel J.F., Zaeytijd, Julie De, Inglehearn, Chris F., Kousal, Bohdan, Leroy, Bart P., Rivolta, Carlo, Vaclavik, Veronika, Ende, Jenneke van den, Schooneveld, Mary J. van, Gómez-Skarmeta, José Luis, Tena, Juan J., Martínez-Morales, Juan Ramón, Liskova, Petra, Vleminckx, Kris, Baere, Elfride De, Ghent University, European Commission, Foundation Fighting Blindness, Research Foundation - Flanders, Sompele, Stijn Van de, Small, Kent W., Burcu Cicekdal, Munevver, López Soriano, Víctor, D’haene, Eva, Shaya, Fadi S., Agemy, Steven, Snickt, Thijs Van der, Dueñas Rey, Alfredo, Rosseel, Toon, Heetvelde, Mattias Van, Vergult, Sarah, Balikova, Irina, Bergen, Arthur A., Boon, Camiel J.F., Zaeytijd, Julie De, Inglehearn, Chris F., Kousal, Bohdan, Leroy, Bart P., Rivolta, Carlo, Vaclavik, Veronika, Ende, Jenneke van den, Schooneveld, Mary J. van, Gómez-Skarmeta, José Luis, Tena, Juan J., Martínez-Morales, Juan Ramón, Liskova, Petra, Vleminckx, Kris, and Baere, Elfride De
- Abstract
North Carolina macular dystrophy (NCMD) is a rare autosomal-dominant disease affecting macular development. The disease is caused by non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications in two distinct chromosomal loci, overlapping DNase I hypersensitive sites near either PRDM13 or IRX1. To unravel the mechanisms by which these variants cause disease, we first established a genome-wide multi-omics retinal database, RegRet. Integration of UMI-4C profiles we generated on adult human retina then allowed fine-mapping of the interactions of the PRDM13 and IRX1 promoters and the identification of eighteen candidate cis-regulatory elements (cCREs), the activity of which was investigated by luciferase and Xenopus enhancer assays. Next, luciferase assays showed that the non-coding SNVs located in the two hotspot regions of PRDM13 affect cCRE activity, including two NCMD-associated non-coding SNVs that we identified herein. Interestingly, the cCRE containing one of these SNVs was shown to interact with the PRDM13 promoter, demonstrated in vivo activity in Xenopus, and is active at the developmental stage when progenitor cells of the central retina exit mitosis, suggesting that this region is a PRDM13 enhancer. Finally, mining of single-cell transcriptional data of embryonic and adult retina revealed the highest expression of PRDM13 and IRX1 when amacrine cells start to synapse with retinal ganglion cells, supporting the hypothesis that altered PRDM13 or IRX1 expression impairs interactions between these cells during retinogenesis. Overall, this study provides insight into the cis-regulatory mechanisms of NCMD and supports that this condition is a retinal enhanceropathy.
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- 2022
32. Gain of gene regulatory network interconnectivity at the origin of vertebrates
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European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Agence Nationale de la Recherche (France), Institut Universitaire de France, Ministry of Science and Technology (Taiwan), Gil-Gálvez, Alejandro, Jiménez-Gancedo, Sandra, Pérez-Posada, Alberto, Franke, Martin, Acemel, Rafael D., Lin, Che-Yi, Chou, Cindy, Su, Yi-Hsien, Yu, Jr-Kai, Bertrand, Stephanie, Schubert, Michael, Escrivá, Héctor, Tena, Juan J., Gómez-Skarmeta, José Luis, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Agence Nationale de la Recherche (France), Institut Universitaire de France, Ministry of Science and Technology (Taiwan), Gil-Gálvez, Alejandro, Jiménez-Gancedo, Sandra, Pérez-Posada, Alberto, Franke, Martin, Acemel, Rafael D., Lin, Che-Yi, Chou, Cindy, Su, Yi-Hsien, Yu, Jr-Kai, Bertrand, Stephanie, Schubert, Michael, Escrivá, Héctor, Tena, Juan J., and Gómez-Skarmeta, José Luis
- Abstract
Signaling pathways control a large number of gene regulatory networks (GRNs) during animal development, acting as major tools for body plan formation [A. Pires-daSilva, R. J. Sommer, Nat. Rev. Genet. 4, 39-49 (2003)], although only a few of these pathways operate during this period [J. J. Sanz-Ezquerro, A. E. Munsterberg, € S. Stricker, Front. Cell Dev. Biol. 5, 76 (2017)]. Moreover, most of them have been largely conserved during metazoan evolution [L. S. Babonis, M. Q. Martindale, Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20150477 (2017)]. How evolution has generated a vast diversity of animal morphologies with such a limited number of tools is still largely unknown. Here, we show that gain of interconnectivity between signaling pathways and the GRNs they control may have critically contributed to the origin of vertebrates. We perturbed the retinoic acid, Wnt, FGF, and Nodal signaling pathways during gastrulation in the invertebrate chordate amphioxus and zebrafish and compared the effects on gene expression and cis-regulatory elements (CREs). We found that multiple developmental genes gain response to these pathways through vertebrate-specific CREs. Moreover, in contrast to amphioxus, many of these CREs responded to multiple pathways in zebrafish, which reflects their high interconnectivity. Furthermore, we found that vertebrate-specific cell types are more enriched in highly interconnected genes than in tissues with more ancient origin. Thus, the increase of CREs in vertebrates integrating inputs from different signaling pathways probably contributed to gene expression complexity and to the formation of new cell types and morphological novelties in this lineage.
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- 2022
33. Pluripotency factors regulate the onset of Hox cluster activation in the early embryo
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Junta de Andalucía, European Research Council, La Caixa, Fundación Ramón Areces, Instituto de Salud Carlos III, Fundación Pro CNIC, Tiana, María, López-Jiménez, Elena, Sainz de Aja, Julio, Barral, Antonio, Victorino, Jesús, Badía-Careaga, Claudio, Rollán, Isabel, Rouco, Raquel, Santos, Elisa, Sánchez-Iranzo, Héctor, Acemel, Rafael D., Torroja, Carlos, Adán, Javier, Andrés-León, Eduardo, Gómez-Skarmeta, José Luis, Giovinazzo, Giovanna, Sánchez-Cabo, Fátima, Manzanares, Miguel, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Junta de Andalucía, European Research Council, La Caixa, Fundación Ramón Areces, Instituto de Salud Carlos III, Fundación Pro CNIC, Tiana, María, López-Jiménez, Elena, Sainz de Aja, Julio, Barral, Antonio, Victorino, Jesús, Badía-Careaga, Claudio, Rollán, Isabel, Rouco, Raquel, Santos, Elisa, Sánchez-Iranzo, Héctor, Acemel, Rafael D., Torroja, Carlos, Adán, Javier, Andrés-León, Eduardo, Gómez-Skarmeta, José Luis, Giovinazzo, Giovanna, Sánchez-Cabo, Fátima, and Manzanares, Miguel
- Abstract
Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs.
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- 2022
34. Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), Fondazione Telethon, National Institutes of Health (US), Centre Hospitalier Universitaire de Liège, Novo Nordisk, European Commission, Université de Liège, Franke, Martin, Daly, Adrian F., Palmeira, Leonor, Tirosh, Amit, Stigliano, Antonio, Trifan, Eszter, Faucz, Fabio R., Abboud, Dayana, Petrossians, Patrick, Tena, Juan J., Vitali, Eleonora, Lania, Andrea G., Gómez-Skarmeta, José Luis, Beckers, Albert, Stratakis, Constantine A., Trivellin, Giampaolo, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), Fondazione Telethon, National Institutes of Health (US), Centre Hospitalier Universitaire de Liège, Novo Nordisk, European Commission, Université de Liège, Franke, Martin, Daly, Adrian F., Palmeira, Leonor, Tirosh, Amit, Stigliano, Antonio, Trifan, Eszter, Faucz, Fabio R., Abboud, Dayana, Petrossians, Patrick, Tena, Juan J., Vitali, Eleonora, Lania, Andrea G., Gómez-Skarmeta, José Luis, Beckers, Albert, Stratakis, Constantine A., and Trivellin, Giampaolo
- Abstract
X-linked acrogigantism (X-LAG) is the most severe form of pituitary gigantism and is characterized by aggressive growth hormone (GH)-secreting pituitary tumors that occur in early childhood. X-LAG is associated with chromosome Xq26.3 duplications (the X-LAG locus typically includes VGLL1, CD40LG, ARHGEF6, RBMX, and GPR101) that lead to massive pituitary tumoral expression of GPR101, a novel regulator of GH secretion. The mechanism by which the duplications lead to marked pituitary misexpression of GPR101 alone was previously unclear. Using Hi-C and 4C-seq, we characterized the normal chromatin structure at the X-LAG locus. We showed that GPR101 is located within a topologically associating domain (TAD) delineated by a tissue-invariant border that separates it from centromeric genes and regulatory sequences. Next, using 4C-seq with GPR101, RBMX, and VGLL1 viewpoints, we showed that the duplications in multiple X-LAG-affected individuals led to ectopic interactions that crossed the invariant TAD border, indicating the existence of a similar and consistent mechanism of neo-TAD formation in X-LAG. We then identified several pituitary active cis-regulatory elements (CREs) within the neo-TAD and demonstrated in vitro that one of them significantly enhanced reporter gene expression. At the same time, we showed that the GPR101 promoter permits the incorporation of new regulatory information. Our results indicate that X-LAG is a TADopathy of the endocrine system in which Xq26.3 duplications disrupt the local chromatin architecture forming a neo-TAD. Rewiring GPR101-enhancer interaction within the new regulatory unit is likely to cause the high levels of aberrant expression of GPR101 in pituitary tumors caused by X-LAG.
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- 2022
35. Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers
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European Commission, Ministerio de Economía y Competitividad (España), Fundació La Marató de TV3, Fundação para a Ciência e a Tecnologia (Portugal), EMBO, Bordeira-Carriço, Renata, Teixeira, Joana, Duque, Marta, Galhardo, Mafalda, Ribeiro, Diogo, Acemel, Rafael D., Firbas, Panos, Tena, Juan J., Eufrásio, Ana, Marques, Joana, Ferreira, Fábio J., Freitas, Telmo, Carnero, Amancio, Gómez-Skarmeta, José Luis, Bessa, José, European Commission, Ministerio de Economía y Competitividad (España), Fundació La Marató de TV3, Fundação para a Ciência e a Tecnologia (Portugal), EMBO, Bordeira-Carriço, Renata, Teixeira, Joana, Duque, Marta, Galhardo, Mafalda, Ribeiro, Diogo, Acemel, Rafael D., Firbas, Panos, Tena, Juan J., Eufrásio, Ana, Marques, Joana, Ferreira, Fábio J., Freitas, Telmo, Carnero, Amancio, Gómez-Skarmeta, José Luis, and Bessa, José
- Abstract
The pancreas is a central organ for human diseases. Most alleles uncovered by genome-wide association studies of pancreatic dysfunction traits overlap with non-coding sequences of DNA. Many contain epigenetic marks of cis-regulatory elements active in pancreatic cells, suggesting that alterations in these sequences contribute to pancreatic diseases. Animal models greatly help to understand the role of non-coding alterations in disease. However, interspecies identification of equivalent cis-regulatory elements faces fundamental challenges, including lack of sequence conservation. Here we combine epigenetic assays with reporter assays in zebrafish and human pancreatic cells to identify interspecies functionally equivalent cis-regulatory elements, regardless of sequence conservation. Among other potential disease-relevant enhancers, we identify a zebrafish ptf1a distal-enhancer whose deletion causes pancreatic agenesis, a phenotype previously found to be induced by mutations in a distal-enhancer of PTF1A in humans, further supporting the causality of this condition in vivo. This approach helps to uncover interspecies functionally equivalent cis-regulatory elements and their potential role in human disease.
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- 2022
36. Regulatory architecture of the RCA gene cluster captures an intragenic TAD boundary, CTCF-Mediated chromatin looping and a long-range intergenic enhancer
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National Institutes of Health (US), Australian Government, University of Western Australia, CSIC-JA-UPO - Centro Andaluz de Biología del Desarrollo (CABD), Cheng, Jessica, Clayton, Joshua S., Acemel, Rafael D., Zheng, Ye, Taylor, Rhonda L., Keleş, Sündüz, Franke, Martin, Boackle, Susan A., Harley, John B., Quail, Elizabeth, Gómez-Skarmeta, José Luis, Ulgiati, Daniela, National Institutes of Health (US), Australian Government, University of Western Australia, CSIC-JA-UPO - Centro Andaluz de Biología del Desarrollo (CABD), Cheng, Jessica, Clayton, Joshua S., Acemel, Rafael D., Zheng, Ye, Taylor, Rhonda L., Keleş, Sündüz, Franke, Martin, Boackle, Susan A., Harley, John B., Quail, Elizabeth, Gómez-Skarmeta, José Luis, and Ulgiati, Daniela
- Abstract
The Regulators of Complement Activation (RCA) gene cluster comprises several tandemly arranged genes with shared functions within the immune system. RCA members, such as complement receptor 2 (CR2), are well-established susceptibility genes in complex autoimmune diseases. Altered expression of RCA genes has been demonstrated at both the functional and genetic level, but the mechanisms underlying their regulation are not fully characterised. We aimed to investigate the structural organisation of the RCA gene cluster to identify key regulatory elements that influence the expression of CR2 and other genes in this immunomodulatory region. Using 4C, we captured extensive CTCF-mediated chromatin looping across the RCA gene cluster in B cells and showed these were organised into two topologically associated domains (TADs). Interestingly, an inter-TAD boundary was located within the CR1 gene at a well-characterised segmental duplication. Additionally, we mapped numerous gene-gene and gene-enhancer interactions across the region, revealing extensive co-regulation. Importantly, we identified an intergenic enhancer and functionally demonstrated this element upregulates two RCA members (CR2 and CD55) in B cells. We have uncovered novel, long-range mechanisms whereby autoimmune disease susceptibility may be influenced by genetic variants, thus highlighting the important contribution of chromatin topology to gene regulation and complex genetic disease.
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- 2022
37. Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements
- Author
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European Commission, Agencia Estatal de Investigación (España), Baranasic, Damir, Hörtenhuber, Matthias, Balwierz, Piotr J., Zehnder, Tobias, Mukarram, Abdul Kadir, Nepal, Chirag, Várnai, Csilla, Hadzhiev, Yavor, Jiménez-González, Ada, Li, Nan, Wragg, Joseph, D’Orazio, Fabio M., Relic, Dorde, Pachkov, Mikhail, Díaz, Noelia, Hernández-Rodríguez, Benjamín, Chen, Zelin, Stoiber, Marcus, Dong, Michaël, Stevens, Irene, Ross, Samuel E., Eagle, Anne, Martin, Ryan, Obasaju, Oluwapelumi, Rastegar, Sepand, McGarvey, Alison C., Kopp, Wolfgang, Chambers, Emily, Wang, Dennis, Kim, Hyejeong R., Acemel, Rafael D., Naranjo, Silvia, Łapiński, Maciej, Chong, Vanessa, Mathavan, Sinnakaruppan, Peers, Bernard, Sauka-Spengler, Tatjana, Vingron, Martin, Carninci, Piero, Ohler, Uwe, Lacadie, Scott Allen, Burgess, Shawn M., Winata, Cecilia, Eeden, Freek van, Vaquerizas Erdocia, Juan Manuel, Gómez-Skarmeta, José Luis, Onichtchouk, Daria, Brown, Ben James, Bogdanovic, Ozren, Nimwegen, Erik van, Westerfield, Monte, Wardle, Fiona C., Daub, Carsten O., Lenhard, Boris, Müller, Ferenc, European Commission, Agencia Estatal de Investigación (España), Baranasic, Damir, Hörtenhuber, Matthias, Balwierz, Piotr J., Zehnder, Tobias, Mukarram, Abdul Kadir, Nepal, Chirag, Várnai, Csilla, Hadzhiev, Yavor, Jiménez-González, Ada, Li, Nan, Wragg, Joseph, D’Orazio, Fabio M., Relic, Dorde, Pachkov, Mikhail, Díaz, Noelia, Hernández-Rodríguez, Benjamín, Chen, Zelin, Stoiber, Marcus, Dong, Michaël, Stevens, Irene, Ross, Samuel E., Eagle, Anne, Martin, Ryan, Obasaju, Oluwapelumi, Rastegar, Sepand, McGarvey, Alison C., Kopp, Wolfgang, Chambers, Emily, Wang, Dennis, Kim, Hyejeong R., Acemel, Rafael D., Naranjo, Silvia, Łapiński, Maciej, Chong, Vanessa, Mathavan, Sinnakaruppan, Peers, Bernard, Sauka-Spengler, Tatjana, Vingron, Martin, Carninci, Piero, Ohler, Uwe, Lacadie, Scott Allen, Burgess, Shawn M., Winata, Cecilia, Eeden, Freek van, Vaquerizas Erdocia, Juan Manuel, Gómez-Skarmeta, José Luis, Onichtchouk, Daria, Brown, Ben James, Bogdanovic, Ozren, Nimwegen, Erik van, Westerfield, Monte, Wardle, Fiona C., Daub, Carsten O., Lenhard, Boris, and Müller, Ferenc
- Abstract
Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals
- Published
- 2022
38. Multi-omics profiling, in vitro and in vivo enhancer assays dissect the cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy
- Author
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Van de Sompele, Stijn, primary, Small, Kent W., additional, Cicekdal, Munevver Burcu, additional, Soriano, Víctor López, additional, D’haene, Eva, additional, Shaya, Fadi S., additional, Agemy, Steven, additional, Van der Snickt, Thijs, additional, Rey, Alfredo Dueñas, additional, Rosseel, Toon, additional, Van Heetvelde, Mattias, additional, Vergult, Sarah, additional, Balikova, Irina, additional, Bergen, Arthur A., additional, Boon, Camiel J. F., additional, De Zaeytijd, Julie, additional, Inglehearn, Chris F., additional, Kousal, Bohdan, additional, Leroy, Bart P., additional, Rivolta, Carlo, additional, Vaclavik, Veronika, additional, van den Ende, Jenneke, additional, van Schooneveld, Mary J., additional, Gómez-Skarmeta, José Luis, additional, Tena, Juan J., additional, Martinez-Morales, Juan R., additional, Liskova, Petra, additional, Vleminckx, Kris, additional, and De Baere, Elfride, additional
- Published
- 2022
- Full Text
- View/download PDF
39. Gain of gene regulatory network interconnectivity at the origin of vertebrates
- Author
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Gil-Gálvez, Alejandro, primary, Jiménez-Gancedo, Sandra, additional, Pérez-Posada, Alberto, additional, Franke, Martin, additional, Acemel, Rafael D., additional, Lin, Che-Yi, additional, Chou, Cindy, additional, Su, Yi-Hsien, additional, Yu, Jr-Kai, additional, Bertrand, Stephanie, additional, Schubert, Michael, additional, Escrivá, Héctor, additional, Tena, Juan J., additional, and Gómez-Skarmeta, José Luis, additional
- Published
- 2022
- Full Text
- View/download PDF
40. Transphyletic conservation of developmental regulatory state in animal evolution
- Author
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Royo, José Luis, Maeso, Ignacio, Irimia, Manuel, Gao, Feng, Peter, Isabelle S., Lopes, Carla S., D'Aniello, Salvatore, Casares, Fernando, Davidson, Eric H., Garcia-Fernández, Jordi, and Gómez-Skarmeta, José Luis
- Published
- 2011
41. El genoma regulador
- Author
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Gómez Skarmeta, José Luis, primary
- Published
- 2018
- Full Text
- View/download PDF
42. Sea urchin developmental gut GRNs through combinatorial omics
- Author
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Voronov, D., Magri, Marta Silvia, Paganos, P., Gómez-Skarmeta, José Luis, Maeso, Ignacio, and Arnone, M. I.
- Abstract
Trabajo presentado en el EMBO Workshop The evolution of animal genomes, celebrado en modalidad virtual del 13 al 17 de septiembre de 2021.
- Published
- 2021
43. Genome evolution in morphological adaptation to cave environment in Astyanax mexicanus
- Author
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Gil-Galvez, Alejandro, Calle-Mustienes, Elisa de la, Neto, Ana, Santana-Molina, Carlos, Triglia, A., Beati, P., Bilandžija, H., Devos, Damien P., Jeffery, W. R., Franchini, L., Tena, Juan J., and Gómez-Skarmeta, José Luis
- Abstract
Trabajo presentado en el EMBO Workshop The evolution of animal genomes, celebrado en modalidad virtual del 13 al 17 de septiembre de 2021.
- Published
- 2021
44. The Shh / Gli3 gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits
- Author
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Letelier, Joaquín, primary, Naranjo, Silvia, additional, Sospedra-Arrufat, Ismael, additional, Martinez-Morales, Juan Ramón, additional, Lopez-Rios, Javier, additional, Shubin, Neil, additional, and Gómez-Skarmeta, José Luis, additional
- Published
- 2021
- Full Text
- View/download PDF
45. Deletion 1q43-44 in a patient with clinical diagnosis of Warburg–Micro syndrome
- Author
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Arroyo-Carrera, Ignacio, de Zaldívar Tristancho, María Solo, Bermejo-Sánchez, Eva, Martínez-Fernández, María Luisa, López-Lafuente, Amparo, MacDonald, Alexandra, Zúñiga, Ángel, Gómez-Skarmeta, José Luis, and Martínez-Frías, María Luisa
- Published
- 2015
- Full Text
- View/download PDF
46. sox21a Directs Lateral Line Patterning by Modulating FGF Signaling
- Author
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Ariza-Cosano, Ana, Bensimon-Brito, Anabela, Gómez-Skarmeta, José Luis, and Bessa, José
- Published
- 2015
- Full Text
- View/download PDF
47. Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish
- Author
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Baranasic, Damir, primary, Hörtenhuber, Matthias, additional, Balwierz, Piotr, additional, Zehnder, Tobias, additional, Mukarram, Abdul Kadir, additional, Nepal, Chirag, additional, Varnai, Csilla, additional, Hadzhiev, Yavor, additional, Jimenez-Gonzalez, Ada, additional, Li, Nan, additional, Wragg, Joseph, additional, D’Orazio, Fabio, additional, Díaz, Noelia, additional, Hernández-Rodríguez, Benjamín, additional, Chen, Zelin, additional, Stoiber, Marcus, additional, Dong, Michaël, additional, Stevens, Irene, additional, Ross, Samuel E., additional, Eagle, Anne, additional, Martin, Ryan, additional, Obasaju, Pelumi, additional, Rastegar, Sepand, additional, McGarvey, Alison C., additional, Kopp, Wolfgang, additional, Chambers, Emily, additional, Wang, Dennis, additional, Kim, Hyejeong R., additional, Acemel, Rafael D., additional, Naranjo, Silvia, additional, Lapinski, Maciej, additional, Chong, Vanessa, additional, Mathavan, Sinnakaruppan, additional, Peers, Bernard, additional, Sauka-Spengler, Tatjana, additional, Vingron, Martin, additional, Carninci, Piero, additional, Ohler, Uwe, additional, Lacadie, Scott Allen, additional, Burgess, Shawn, additional, Winata, Cecilia, additional, van Eeden, Freek, additional, Vaquerizas, Juan M., additional, Gómez-Skarmeta, José Luis, additional, Onichtchouk, Daria, additional, Brown, Ben James, additional, Bogdanovic, Ozren, additional, Westerfield, Monte, additional, Wardle, Fiona C., additional, Daub, Carsten O., additional, Lenhard, Boris, additional, and Müller, Ferenc, additional
- Published
- 2021
- Full Text
- View/download PDF
48. The role of Cis-Regulatory elements in morphological adaptation to cave environment in Astyanax mexicanus
- Author
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Gil-Galvez, Alejandro, Calle-Mustienes, Elisa de la, Neto, Ana, Santana-Molina, Carlos, Triglia, A., Beati, P., Bilandžija, H., Devos, Damien P., Jeffery, W. R., Franchini, L., Tena, Juan J., and Gómez-Skarmeta, José Luis
- Abstract
Trabajo presentado en EMBO Workshop Enhanceropathies: Understanding enhancer function to understand human disease, celebrado en Santander (España) del 06 al 09 de octubre de 2021.
- Published
- 2021
49. Deciphering the gene regulatory network of retinoic acid signaling during zebrafish embryonic development
- Author
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Gallardo-Fuentes, Lourdes, Moreno Oñate, Marta, Jiménez-Gancedo, Sandra, Tena, Juan J., Gómez-Skarmeta, José Luis, and Santos-Pereira, José M.
- Abstract
Trabajo presentado en EMBO Workshop The evolution of animal genomes, celebrado en modalidad virtual del 13 al 17 de septiembre de 2021., Retinoic acid (RA) is the active form of retinol (vitamin A) and functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements (RAREs). RA signaling is required for embryonic development in chordate animals, being involved in multiple processes, such as body axis extension, hindbrain antero-posterior (AP) patterning, differentiation of neuro-mesodermal progenitors, heart AP patterning and forelimb bud initiation, among others. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during embryonic development. Here we use ChIP-seq to profile the genomic binding of RAR in zebrafish embryos at different developmental stages. Stimulating the RA pathway by treating embryos with all-trans-RA (atRA), the most abundant form of RA, we use a combination of RNA-seq, ATAC-seq and ChIP-seq to gain insight into the mechanisms by which RA signaling control the expression of direct and indirect target genes during early development. Finally, we explore the interplay between RA signaling, Hox and Meis transcription factors, which have been proposed to cooperate during axial skeleton AP patterning. Our results provide new clues about the crosstalk between signaling pathways and transcription factors during vertebrate embryonic development.
- Published
- 2021
50. Developmental dynamics of sea urchin and sea star cis-regulation and the evolution of echinoderm genome organization
- Author
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Magri, Marta Silvia, Voronov, D., Foley, S., Franke, Martin, Cuomo, C., Gil-Galvez, Alejandro, Acemel, Rafael D., Paganos, P., Rancelovic, J., Firbas, Panos, Hinman, V. F., Arnone, M. I., Maeso, Ignacio, and Gómez-Skarmeta, José Luis
- Abstract
Trabajo presentado en EMBO Workshop The evolution of animal genomes, celebrado en modalidad virtual del 13 al 17 de septiembre de 2021.
- Published
- 2021
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