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1. Sox2 is required for embryonic development of the ventral telencephalon through the activation of the ventral determinants Nkx2.1 and Shh.

Author

Ferri A, Favaro R, Beccari L, Bertolini J, Mercurio S, Nieto-Lopez F, Verzeroli C, La Regina F, De Pietri Tonelli D, Ottolenghi S, Bovolenta P, and Nicolis SK

Subjects
Animals, Cells, Cultured, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Hedgehog Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nuclear Proteins metabolism, Pregnancy, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Telencephalon metabolism, Thyroid Nuclear Factor 1, Transcription Factors metabolism, Transcriptional Activation genetics, Body Patterning genetics, Embryonic Development genetics, Hedgehog Proteins genetics, Nuclear Proteins genetics, SOXB1 Transcription Factors physiology, Telencephalon embryology, Transcription Factors genetics
Abstract

The Sox2 transcription factor is active in stem/progenitor cells throughout the developing vertebrate central nervous system. However, its conditional deletion at E12.5 in mouse causes few brain developmental problems, with the exception of the postnatal loss of the hippocampal radial glia stem cells and the dentate gyrus. We deleted Sox2 at E9.5 in the telencephalon, using a Bf1-Cre transgene. We observed embryonic brain defects that were particularly severe in the ventral, as opposed to the dorsal, telencephalon. Important tissue loss, including the medial ganglionic eminence (MGE), was detected at E12.5, causing the subsequent impairment of MGE-derived neurons. The defect was preceded by loss of expression of the essential ventral determinants Nkx2.1 and Shh, and accompanied by ventral spread of dorsal markers. This phenotype is reminiscent of that of mice mutant for the transcription factor Nkx2.1 or for the Shh receptor Smo. Nkx2.1 is known to mediate the initial activation of ventral telencephalic Shh expression. A partial rescue of the normal phenotype at E14.5 was obtained by administration of a Shh agonist. Experiments in Medaka fish indicate that expression of Nkx2.1 is regulated by Sox2 in this species also. We propose that Sox2 contributes to Nkx2.1 expression in early mouse development, thus participating in the region-specific activation of Shh, thereby mediating ventral telencephalic patterning induction.

Published
2013
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2. The transcription factor encyclopedia.

Author

Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XY, Dickman CT, Fulton DL, Lim JS, Schnabl JM, Ramos OH, Vasseur-Cognet M, de Leeuw CN, Simpson EM, Ryffel GU, Lam EW, Kist R, Wilson MS, Marco-Ferreres R, Brosens JJ, Beccari LL, Bovolenta P, Benayoun BA, Monteiro LJ, Schwenen HD, Grontved L, Wederell E, Mandrup S, Veitia RA, Chakravarthy H, Hoodless PA, Mancarelli MM, Torbett BE, Banham AH, Reddy SP, Cullum RL, Liedtke M, Tschan MP, Vaz M, Rizzino A, Zannini M, Frietze S, Farnham PJ, Eijkelenboom A, Brown PJ, Laperrière D, Leprince D, de Cristofaro T, Prince KL, Putker M, del Peso L, Camenisch G, Wenger RH, Mikula M, Rozendaal M, Mader S, Ostrowski J, Rhodes SJ, Van Rechem C, Boulay G, Olechnowicz SW, Breslin MB, Lan MS, Nanan KK, Wegner M, Hou J, Mullen RD, Colvin SC, Noy PJ, Webb CF, Witek ME, Ferrell S, Daniel JM, Park J, Waldman SA, Peet DJ, Taggart M, Jayaraman PS, Karrich JJ, Blom B, Vesuna F, O'Geen H, Sun Y, Gronostajski RM, Woodcroft MW, Hough MR, Chen E, Europe-Finner GN, Karolczak-Bayatti M, Bailey J, Hankinson O, Raman V, LeBrun DP, Biswal S, Harvey CJ, DeBruyne JP, Hogenesch JB, Hevner RF, Héligon C, Luo XM, Blank MC, Millen KJ, Sharlin DS, Forrest D, Dahlman-Wright K, Zhao C, Mishima Y, Sinha S, Chakrabarti R, Portales-Casamar E, Sladek FM, Bradley PH, and Wasserman WW

Subjects
Access to Information, Animals, Encyclopedias as Topic, Humans, Internet, Mice, Rats, Transcription, Genetic, Computational Biology, Databases, Protein supply & distribution, Transcription Factors genetics
Abstract

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

Published
2012
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3. Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6.

Author

Conte I, Marco-Ferreres R, Beccari L, Cisneros E, Ruiz JM, Tabanera N, and Bovolenta P

Subjects
Amacrine Cells metabolism, Animals, Animals, Genetically Modified, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Differentiation genetics, Chromatin Immunoprecipitation, Gene Expression, Neurons metabolism, Oryzias genetics, Oryzias metabolism, Photoreceptor Cells, Retina cytology, Retina metabolism, Retinal Ganglion Cells metabolism, Rhodopsin genetics, Rhodopsin metabolism, Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Transcription Factors metabolism
Abstract

Timely generation of distinct neural cell types in appropriate numbers is fundamental for the generation of a functional retina. In vertebrates, the transcription factor Six6 is initially expressed in multipotent retina progenitors and then becomes restricted to differentiated retinal ganglion and amacrine cells. How Six6 expression in the retina is controlled and what are its precise functions are still unclear. To address this issue, we used bioinformatic searches and transgenic approaches in medaka fish (Oryzias latipes) to characterise highly conserved regulatory enhancers responsible for Six6 expression. One of the enhancers drove gene expression in the differentiating and adult retina. A search for transcription factor binding sites, together with luciferase, ChIP assays and gain-of-function studies, indicated that NeuroD, a bHLH transcription factor, directly binds an 'E-box' sequence present in this enhancer and specifically regulates Six6 expression in the retina. NeuroD-induced Six6 overexpression in medaka embryos promoted unorganized retinal progenitor proliferation and, most notably, impaired photoreceptor differentiation, with no apparent changes in other retinal cell types. Conversely, Six6 gain- and loss-of-function changed NeuroD expression levels and altered the expression of the photoreceptor differentiation marker Rhodopsin. In addition, knockdown of Six6 interfered with amacrine cell generation. Together, these results indicate that Six6 and NeuroD control the expression of each other and their functions coordinate amacrine cell generation and photoreceptor terminal differentiation.

Published
2010
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4. Dbx2 regulation in limbs suggests interTAD sharing of enhancers.

Author

Beccari, Leonardo, Jaquier, Gabriel, Lopez‐Delisle, Lucille, Rodriguez‐Carballo, Eddie, Mascrez, Bénédicte, Gitto, Sandra, Woltering, Joost, and Duboule, Denis

Subjects
HOMEOBOX genes, GENE silencing, PROTEIN binding, PHENOTYPES, TRANSCRIPTION factors
Abstract

Background: During tetrapod limb development, the HOXA13 and HOXD13 transcription factors are critical for the emergence and organization of the autopod, the most distal aspect where digits will develop. Since previous work had suggested that the Dbx2 gene is a target of these factors, we set up to analyze in detail this potential regulatory interaction. Results: We show that HOX13 proteins bind to mammalian‐specific sequences at the vicinity of the Dbx2 locus that have enhancer activity in developing digits. However, the functional inactivation of the DBX2 protein did not elicit any particular phenotype related to Hox genes inactivation in digits, suggesting either redundant or compensatory mechanisms. We report that the neighboring Nell2 and Ano6 genes are also expressed in distal limb buds and are in part controlled by the same Dbx2 enhancers despite being localized into two different topologically associating domains (TADs) flanking the Dbx2 locus. Conclusions: We conclude that Hoxa13 and Hoxd genes cooperatively activate Dbx2 expression in developing digits through binding to mammalian specific regulatory sequences in the Dbx2 neighborhood. Furthermore, these enhancers can overcome TAD boundaries in either direction to co‐regulate a set of genes located in distinct chromatin domains. Key Findings: Hoxa13 and Hoxd genes cooperatively regulate Dbx2 expression in developing digits via eutherian specific enhancers.Dbx2 is expressed in different digit joint precursors but its function there is not essential.Dbx2 enhancers also control the expression of the Nell2 and Ano6 genes, which are located in different TADs, thus overcoming the boundary effect.Dbx2 chromatin architecture and enhancers evolved in the mammalian lineage. [ABSTRACT FROM AUTHOR]

Published
2021
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5. The Transcription Factor Encyclopedia

Author

Yusuf, Dimas, Butland, Stefanie L., Swanson, Magdalena I., Bolotin, Eugene, Ticoll, Amy, Cheung, Warren A., Zhang, Xiao Yu Cindy, Dickman, Christopher T. D., Fulton, Debra L., Lim, Jonathan S., Schnabl, Jake M., Ramos, Oscar H. P., Vasseur-Cognet, Mireille, de Leeuw, Charles N., Simpson, Elizabeth M., Ryffel, Gerhart U., Lam, Eric W.-F., Kist, Ralf, Wilson, Miranda S. C., Marco-Ferreres, Raquel, Brosens, Jan J., Beccari, Leonardo L., Bovolenta, Paola, Benayoun, Bérénice A., Monteiro, Lara J, Schwenen, Helma D C, Grontved, Lars, Wederell, Elizabeth, Mandrup, Susanne, Veitia, Reiner A, Chakravarthy, Harini, Hoodless, Pamela A., Mancarelli, M Michela, Torbett, Bruce E, Banham, Alison H, Reddy, Sekhar P, Cullum, Rebecca L, Liedtke, Michaela, Tschan, Mario P, Vaz, Michelle, Rizzino, Angie, Zannini, Mariastella, Frietze, Seth, Farnham, Peggy J, Eijkelenboom, Astrid, Brown, Philip J, Laperrière, David, Leprince, Dominique, de Cristofaro, Tiziana, Prince, Kelly L, Putker, Marrit, del Peso, Luis, Camenisch, Gieri, Wenger, Roland H, Mikula, Michal, Rozendaal, Marieke, Mader, Sylvie, Ostrowski, Jerzy, Rhodes, Simon J, Van Rechem, Capucine, Boulay, Gaylor, Olechnowicz, Sam W Z, Breslin, Mary B, Lan, Michael S, Nanan, Kyster K, Wegner, Michael, Hou, Juan, Mullen, Rachel D, Colvin, Stephanie C, Noy, Peter John, Webb, Carol F, Witek, Matthew E, Ferrell, Scott, Daniel, Juliet M, Park, Jason, Waldman, Scott A, Peet, Daniel J, Taggart, Michael, Jayaraman, Padma-Sheela, Karrich, Julien J, Blom, Bianca, Vesuna, Farhad, O'Geen, Henriette, Sun, Yunfu, Gronostajski, Richard M, Woodcroft, Mark W, Hough, Margaret R, Chen, Edwin, Europe-Finner, G Nicholas, Karolczak-Bayatti, Magdalena, Bailey, Jarrod, Hankinson, Oliver, Raman, Venu, LeBrun, David P, Biswal, Shyam, Harvey, Christopher J, DeBruyne, Jason P, Hogenesch, John B, Hevner, Robert F, Héligon, Christophe, Luo, Xin M, Blank, Marissa Cathleen, Millen, Kathleen Joyce, Sharlin, David S, Forrest, Douglas, Dahlman-Wright, Karin, Zhao, Chunyan, Mishima, Yuriko, Sinha, Satrajit, Chakrabarti, Rumela, Portales-Casamar, Elodie, Sladek, Frances M, Bradley, Philip H, Wasserman, Wyeth W, Cindy Zhang, Xiao, Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Evaluation and Research Services, Fraser Health Authority, Children's Hospital Oakland, Oakland Research Institute, Computational Biology Program, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Department of Bioinformatics, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Department of Biology, University of Western Ontario (UWO), Genetics Program, Department of Cell Biology and Neuroscience [Riverside] (CBNS), University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut für Zellbiologie, Universität Duisburg-Essen [Essen]-Universitätsklinikum Essen, Department of Surgery and Cancer, Imperial College London-Division of Cancer, Centre for Oral Health Research, Newcastle University [Newcastle]-Medical School-School of Dental Sciences, Department of Development and Differentiation, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Division of Reproductive Health, University of Warwick [Coventry]-Warwick Medical School, University of Warwick [Coventry], Neurobiologia Molecular Celular y del desarrollo, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-Provincial Health Services Authority, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, Department of Molecular Experimental Medicine, The Scripps Research Institute [La Jolla, San Diego], Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences (MEM 131), Nuffield Department of Clinical Laboratory Sciences, University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, Department of Pediatrics, College of Medicine-Department of pediatrics-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Division of Hematology [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Medicine, University of Bern, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine, Institute of Experimental Endocrinology and Oncology (IEOS), Consiglio Nazionale delle Ricerche (CNR), University of Southern California (USC)-Norris Comprehensive Cancer Center, Department of Molecular Cancer Research, University Medical Center [Utrecht]-Utrecht University [Utrecht], University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Molecular Targeting in Breast Cancer research unit, Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Physiological Chemistry, Department of Biochemistry, Universidad Autónoma de Madrid (UAM)-School of Medicine, Institute of Physiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Department of Oncological Genetics, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC)-Medical Center of Postgraduate Education [Warsaw] (MCPE), Indiana University [Bloomington], Indiana University System-Indiana University System-School of Science, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston]-Cancer Center, University of Adelaide-School of Molecular and Biomedical Science, Department of Pediatrics and Biochemistry and Molecular Biology, Louisiana State University (LSU)-Research Institute for Children-Children's Hospital at New Orleans, Departments of Pediatrics and Genetics, Department of Pathology and Molecular Medicine, Queen's University [Kingston, Canada]-Queen's Cancer Research Institute, School of Medicine [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Institut fuer Biochemie-Emil-Fischer-Zentrum, Department of Molecular Biology and Biochemistry, University Indianapolis-Indiana University School of Medicine, Department of Immunity and Infection, School of Medical and Dental Sciences-University of Birmingham [Birmingham], Immunobiology and Cancer Program, Oklahoma Medical Research Foundation (OMRF), Radiation Oncology, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospitals, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), McMaster University [Hamilton, Ontario], School of Medicine, Johns Hopkins University (JHU), Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University-Jefferson Medical College, Discipline of Biochemistry, Institute of Cellular Medicine, Newcastle University [Newcastle]-Faculty of Medicine-Medical School, Department of Immunity and Immunology, Department of Cell Biology and Histology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Immunology Amsterdam, Division of Cancer Imaging Research, Johns Hopkins University (JHU)-School of Medicine-Department of Radiology, Genome Center [UC Davis], University of California [Davis] (UC Davis), School of Biological Sciences [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), Department of Biochemistry and Developmental Genomics Group, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY)-State University of New York (SUNY)-Center of Excellence in Bioinformatics and Life Sciences, Department of Molecular and Cellular Biology, University of Toronto-Sunnybrook Health Sciences Centre-Department of Laboratory Medicine and Pathobiology, Faculty of Medical Sciences, Newcastle University [Newcastle]-Medical School-Institute of Cellular Medicine, Department of Pathology and Laboratory Medicine, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Radiology and Oncology, Johns Hopkins University (JHU)-School of Medicine, Department of Environmental Health Sciences, Johns Hopkins University (JHU)-Johns Hopkins Bloomberg School of Public Health [Baltimore], Department of Pharmacology and Toxicology, Neuroscience Institute-Morehouse School of Medicine, Department of Pharmacology, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Department of Neurological Surgery, University of Washington [Seattle]-Seattle Children's Research Institute, Faculty of Biology and Medicine, Université de Lausanne = University of Lausanne (UNIL)-Center for Integrated Genomics, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University [Blacksburg]-Virginia-Maryland College of Veterinary Medicine, Department of Molecular Genetics and Cell Biology, University of Illinois [Chicago] (UIC), Center for Integrative Brain Research, University of Washington [Seattle], Clinical Endocrinology Branch, National Institutes of Health (NIH)-National Institute of Diabetes, Digestive, and Kidney Disorders, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], State University of New York (SUNY)-State University of New York (SUNY), BMC, Ed., Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-Universitätsklinikum Essen, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), UAM. Departamento de Bioquímica, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), Fred Hutchinson Cancer Research Center [Seattle] ( FHCRC ) -Public Health Sciences Division, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), University of Western Ontario ( UWO ), Department of Cell Biology and Neuroscience [Riverside] ( CBNS ), University of California [Riverside] ( UCR ), Service d'Ingénierie Moléculaire des Protéines ( SIMOPRO ), Département Médicaments et Technologies pour la Santé ( DMTS ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CIBER de Enfermedades Raras (CIBERER)-Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO)-CIBER de Enfermedades Raras (CIBERER), Service de Pathologies moléculaire et cellulaire, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), UNIVERSITY OF SOUTHERN DENMARK, BC Cancer Agency ( BCCRC ) -Provincial Health Services Authority, Scripps Research Institute, Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences ( MEM 131 ), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, College of Medicine-Department of pediatrics-University of Illinois at Chicago ( UIC ), Department of Medicine/Hematology, Stanford University School of Medicine, Institute of Experimental Endocrinology and Oncology ( IEOS ), CNR - National Research Council, University of Southern California ( USC ) -Norris Comprehensive Cancer Center, Utrecht University [Utrecht]-University Medical Center Utrecht, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Université de Montréal-Institute for Research in Immunology and Cancer, Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Lille, Droit et Santé, Utrecht University [Utrecht]-University Medical Centre Utrecht, Universidad Autonoma de Madrid ( UAM ) -School of Medicine, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ) -Medical Center of Postgraduate Education [Warsaw] ( MCPE ), Indiana University [Bloomington]-School of Science, Harvard Medical School [Boston] ( HMS ) -Cancer Center-Massachusetts General Hospital, Louisiana State University Health Sciences Center-Research Institute for Children-Children's Hospital at New Orleans, Queen's University [Kingston]-Queen's Cancer Research Institute, Institut fuer Biochemie-Emil-Fischer-Zentrum-Friedrich-Alexander Universitaet Erlangen-Nuernberg, Indiana University School of Medicine-University Indianapolis, Oklahoma Medical Research Foundation, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospital, University of Oklahoma Health Sciences Center ( OUHSC ), Johns Hopkins University ( JHU ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Center for Immunology Amsterdam, Johns Hopkins University ( JHU ) -School of Medicine-Department of Radiology, University of California at Davis, Division of Biological Sciences [San Diego], University of California [San Diego] ( UC San Diego ), State University of New York at Buffalo ( SUNY Buffalo ) -Center of Excellence in Bioinformatics and Life Sciences, University of California at Los Angeles [Los Angeles] ( UCLA ) -David Geffen School of Medicine, Johns Hopkins University ( JHU ) -School of Medicine, Johns Hopkins University ( JHU ) -Johns Hopkins Bloomberg School of Public Health, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Lausanne-Center for Integrated Genomics, Virginia Polytechnic Institute and State University [Blacksburg]-VA-MD Regional College of Veterinary Medicine, University of Illinois at Chicago ( UIC ), State University of New York at Buffalo ( SUNY Buffalo ) -University of Buffalo School of Medicine and Biomedical Sciences, University of California [Riverside] (UCR), University of California-University of California, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University School of Medicine-The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], Utrecht University [Utrecht]-University Medical Center [Utrecht], Universidad Autonoma de Madrid (UAM)-School of Medicine, Cancer Center-Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Emil-Fischer-Zentrum-Institut fuer Biochemie, School of Molecular and Biomedical Science-University of Adelaide, School of Medicine-Department of Radiology-Johns Hopkins University (JHU), University of California-University of California-David Geffen School of Medicine [Los Angeles], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), University of Pennsylvania [Philadelphia], Université de Lausanne (UNIL)-Center for Integrated Genomics, AII - Amsterdam institute for Infection and Immunity, and Cell Biology and Histology

Subjects
Encyclopedias as Topic, INFORMATION, WIKI, Transcription, Genetic, 05 Environmental Sciences, Medizin, [SDV.GEN] Life Sciences [q-bio]/Genetics, Automate Content, Web API, ANNOTATION, Mini review, Mice, 0302 clinical medicine, Portable Document Format, GENETICS & HEREDITY, Databases, Protein, Informática, 0303 health sciences, PROTEIN DATA-BANK, Application programming interface, BIOTECHNOLOGY & APPLIED MICROBIOLOGY, MENDELIAN-INHERITANCE, ddc:57, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Application Programming Interface, Encyclopedia, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], The Internet, Transcription (software), Transcription, Life Sciences & Biomedicine, KNOWLEDGEBASE, Medicina, DATABASE, Bioinformatics, Biology, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Zellbiologie (Tumorforschung), World Wide Web, Access to Information, 03 medical and health sciences, Databases, Genetic, Protein Data Bank, ddc:570, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:61, Animals, Humans, ddc:610, MeSH Term, Transcription factor, 030304 developmental biology, Internet, 08 Information And Computing Sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, GENE-REGULATION, business.industry, Protein, Computational Biology, 06 Biological Sciences, Compendium, EVOLUTION, Rats, Evolutionary biology, UPDATE, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Software, Transcription Factors
Abstract

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

Published
2012

6. A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish.

Author

Beccari, Leonardo, Marco-Ferreres, Raquel, Tabanera, Noemi, Manfredi, Anna, Souren, Marcel, Wittbrodt, Beate, Conte, Ivan, Wittbrodt, Jochen, and Bovolenta, Paola

Subjects
*PROSENCEPHALON, *CHROMATIN, *IMMUNOPRECIPITATION, *GENETIC regulation, *TRANSCRIPTION factors
Abstract

A well integrated and hierarchically organized gene regulatory network is responsible for the progressive specification of the forebrain. The transcription factor Six3 is one of the central components of this network. As such, Six3 regulates several components of the network, but its upstream regulators are still poorly characterized. Here we have systematically identified such regulators, taking advantage of the detailed functional characterization of the regulatory region of the medaka fish Six3.2 ortholog and of a time/cost-effective trans-regulatory screening, which complemented and overcame the limitations of in silico prediction approaches. The candidates resulting from this search were validated with dose-response luciferase assays and expression pattern criteria. Reconfirmed candidates with a matching expression pattern were also tested with chromatin immunoprecipitation and functional studies. Our results confirm the previously proposed direct regulation of Pax6 and further demonstrate that Msx2 and Pbx1 are bona fide direct regulators of early Six3.2 distribution in distinct domains of the medaka fish forebrain. They also point to other transcription factors, including Tcf3, as additional regulators of different spatial- temporal domains of Six3.2 expression. The activity of these regulators is discussed in the context of the gene regulatory network proposed for the specification of the forebrain. [ABSTRACT FROM AUTHOR]

Published
2015
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7. Meis1 coordinates a network of genes implicated in eye development and microphthalmia.

Author

Marcos, Séverine, González-Lázaro, Monica, Beccari, Leonardo, Carramolino, Laura, Martin-Bermejo, Maria Jesus, Amarie, Oana, Martín, Daniel Mateos-San, Torroja, Carlos, Bogdanović, Ozren, Doohan, Roisin, Puk, Oliver, de Angelis, Martin Hrabê, Graw, Jochen, Gomez-Skarmeta, Jose Luis, Casares, Fernando, Torres, Miguel, and Bovolenta, Paola

Subjects
TRANSCRIPTION factors, MICROPHTHALMIA, ANIMAL models in research, GENE expression, EYE-sockets
Abstract

Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degree. Sporadic and hereditary microphthalmos have been associated with heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adultmice. By combining analysis of Meis1 loss-offunction and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to its preferential association with Hox-Pbx BSs in the trunk, Meis1 binds to Hox/Pbxindependent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1-/- embryos boundaries among the different eye territories are shifted or blurred. We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. [ABSTRACT FROM AUTHOR]

Published
2015
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8. The logic of gene regulatory networks in early vertebrate forebrain patterning

Author

Beccari, Leonardo, Marco-Ferreres, Raquel, and Bovolenta, Paola

Subjects
*GENE regulatory networks, *VERTEBRATES, *PROSENCEPHALON, *SENSORIMOTOR integration, *NEUROBIOLOGISTS, *TRANSCRIPTION factors, *HOMEOSTASIS, *MORPHOGENESIS
Abstract

Abstract: The vertebrate forebrain or prosencephalon is patterned at the beginning of neurulation into four major domains: the telencephalic, hypothalamic, retinal and diencephalic anlagen. These domains will then give rise to the majority of the brain structures involved in sensory integration and the control of higher intellectual and homeostatic functions. Understanding how forebrain pattering arises has thus attracted the interest of developmental neurobiologists for decades. As a result, most of its regulators have been identified and their hierarchical relationship is now the object of active investigation. Here, we summarize the main morphogenetic pathways and transcription factors involved in forebrain specification and propose the backbone of a possible gene regulatory network (GRN) governing its specification, taking advantage of the GRN principles elaborated by pioneer studies in simpler organisms. We will also discuss this GRN and its operational logic in the context of the remarkable morphological and functional diversification that the forebrain has undergone during evolution. [Copyright &y& Elsevier]

Published
2013
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9. Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning.

Author

Beccari, Leonardo, Conte, Ivan, Cisneros, Elsa, and Bovolenta, Paola

Subjects
*PROSENCEPHALON, *GASTRULATION, *TELENCEPHALON, *RETINAL (Visual pigment), *TRANSCRIPTION factors, *HOMEOBOX genes
Abstract

The vertebrate forebrain is patterned during gastrulation into telencephalic, retinal, hypothalamic and diencephalic primordia. Specification of each of these domains requires the concerted activity of combinations of transcription factors (TFs). Paradoxically, some of these factors are widely expressed in the forebrain, which raises the question of how they can mediate regional differences. To address this issue, we focused on the homeobox TF Six3.2. With genomic and functional approaches we demonstrate that, in medaka fish, Six3.2 regulates, in a concentration-dependent manner, telencephalic and retinal specification under the direct control of Sox2. Six3.2 and Sox2 have antagonistic functions in hypothalamic development. These activities are, in part, executed by Foxg1 and Rx3, which seem to be differentially and directly regulated by Six3.2 and Sox2. Together, these data delineate the mechanisms by which Six3.2 diversifies its activity in the forebrain and highlight a novel function for Sox2 as one of the main regulators of anterior forebrain development. They also demonstrate that graded levels of the same TF, probably operating in partially independent transcriptional networks, pattern the vertebrate forebrain along the anterior-posterior axis. [ABSTRACT FROM AUTHOR]

Published
2012
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