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966 results on '"Dekker, Job"'

104. A cohesin traffic pattern genetically linked to gene regulation

Author

Valton, Anne-Laure, primary, Venev, Sergey V., additional, Mair, Barbara, additional, Khokhar, Eraj, additional, Tong, Amy H. Y., additional, Usaj, Matej, additional, Chan, Katherine S. K., additional, Pai, Athma A., additional, Moffat, Jason, additional, and Dekker, Job, additional

Published
2021
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107. Systematic evaluation of chromosome conformation capture assays

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Akgol Oksuz, Betul, Yang, Liyan, Abraham, Sameer, Venev, Sergey V, Krietenstein, Nils, Parsi, Krishna Mohan, Ozadam, Hakan, Oomen, Marlies E, Nand, Ankita, Mao, Hui, Genga, Ryan MJ, Maehr, Rene, Rando, Oliver J, Mirny, Leonid A, Gibcus, Johan H, Dekker, Job, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Akgol Oksuz, Betul, Yang, Liyan, Abraham, Sameer, Venev, Sergey V, Krietenstein, Nils, Parsi, Krishna Mohan, Ozadam, Hakan, Oomen, Marlies E, Nand, Ankita, Mao, Hui, Genga, Ryan MJ, Maehr, Rene, Rando, Oliver J, Mirny, Leonid A, Gibcus, Johan H, and Dekker, Job

Abstract

Chromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.

Published
2021

108. Expanded encyclopaedias of DNA elements in the human and mouse genomes

Author

Moore, Jill E., Purcaro, Michael J., Pratt, Henry E., Epstein, Charles B., Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A., Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L., Freese, Peter Dale, Gorkin, David U., Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A., Mortazavi, Ali, Keller, Cheryl A., Zhang, Xiao-Ou, Elhajjajy, Shaimae I., Huey, Jack, Dickel, Diane E., Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B., Zhang, Jialing, Victorsen, Alec, White, Kevin P., Visel, Axel, Yeo, Gene W., Burge, Christopher B, Lécuyer, Eric, Gilbert, David M., Dekker, Job, Rinn, John, Mendenhall, Eric M., Ecker, Joseph R., Kellis, Manolis, Klein, Robert J., Noble, William S., Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J., Cherry, J. Michael, Myers, Richard M., Ren, Bing, Graveley, Brenton R., Gerstein, Mark B., Pennacchio, Len A., Snyder, Michael P., Bernstein, Bradley E., Wold, Barbara, Hardison, Ross C., Gingeras, Thomas R., Stamatoyannopoulos, John A., Weng, Zhiping, Moore, Jill E., Purcaro, Michael J., Pratt, Henry E., Epstein, Charles B., Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A., Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L., Freese, Peter Dale, Gorkin, David U., Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A., Mortazavi, Ali, Keller, Cheryl A., Zhang, Xiao-Ou, Elhajjajy, Shaimae I., Huey, Jack, Dickel, Diane E., Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B., Zhang, Jialing, Victorsen, Alec, White, Kevin P., Visel, Axel, Yeo, Gene W., Burge, Christopher B, Lécuyer, Eric, Gilbert, David M., Dekker, Job, Rinn, John, Mendenhall, Eric M., Ecker, Joseph R., Kellis, Manolis, Klein, Robert J., Noble, William S., Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J., Cherry, J. Michael, Myers, Richard M., Ren, Bing, Graveley, Brenton R., Gerstein, Mark B., Pennacchio, Len A., Snyder, Michael P., Bernstein, Bradley E., Wold, Barbara, Hardison, Ross C., Gingeras, Thomas R., Stamatoyannopoulos, John A., and Weng, Zhiping

Abstract

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes., NIH (Grants U01HG007019, U01HG007033, U01HG007036, U01HG007037, U41HG006992, U41HG006993, U41HG006994, U41HG006995, U41HG006996, U41HG006997, U41HG006998, U41HG006999, U41HG007000, U41HG007001, U41HG007002, U41HG007003, U54HG006991, U54HG006997, U54HG006998, U54HG007004, U54HG007005, U54HG007010 and UM1HG009442)

Published
2021

109. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research., Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...]

Published
2012
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110. The accessible chromatin landscape of the human genome

Author

Thurman, Robert E., Rynes, Eric, Humbert, Richard, Vierstra, Jeff, Maurano, Matthew T., Haugen, Eric, Sheffield, Nathan C., Stergachis, Andrew B., Vernot, Benjamin, Garg, Kavita, John, Sam, Sandstrom, Richard, Bates, Daniel, Boatman, Lisa, Canfield, Theresa K., Diegel, Morgan, Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Giste, Erika, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tanya, Lajoie, Bryan, Lee, Bum-Kyu, Lee, Kristen, London, Darin, Lotakis, Dimitra, Neph, Shane, Neri, Fidencio, Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Safi, Alexias, Sanchez, Minerva E., Sanyal, Amartya, Shafer, Anthony, Simon, Jeremy M., Song, Lingyun, Vong, Shinny, Weaver, Molly, Yan, Yongqi, Zhang, Zhancheng, Zhang, Zhuzhu, Lenhard, Boris, Tewari, Muneesh, Dorschner, Michael O., Hansen, R. Scott, Navas, Patrick A., Stamatoyannopoulos, George, Iyer, Vishwanath R., Lieb, Jason D., Sunyaev, Shamil R., Akey, Joshua M., Sabo, Peter J., Kaul, Rajinder, Furey, Terrence S., Dekker, Job, Crawford, Gregory E., and Stamatoyannopoulos, John A.

Subjects
Chromatin -- Physiological aspects, DNA -- Physiological aspects, Genetic research, Human genome -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify [similar]2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect [similar]580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation., Author(s): Robert E. Thurman [1, 13]; Eric Rynes [1, 13]; Richard Humbert [1, 13]; Jeff Vierstra [1]; Matthew T. Maurano [1]; Eric Haugen [1]; Nathan C. Sheffield [2]; Andrew B. [...]

Published
2012
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111. The long-range interaction landscape of gene promoters

Author

Sanyal, Amartya, Lajoie, Bryan R., Jain, Gaurav, and Dekker, Job

Subjects
Primers (Molecular genetics) -- Properties, Chromatin -- Properties, Promoters (Genetics) -- Properties, Protein-protein interactions -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The vast non-coding portion of the human genome is full of functional elements and disease-causing regulatory variants. The principles defining the relationships between these elements and distal target genes remain [...]

Published
2012
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112. Spatial partitioning of the regulatory landscape of the X-inactivation centre

Author

Nora, Elphege P., Lajoie, Bryan R., Schulz, Edda G., Giorgetti, Luca, Okamoto, Ikuhiro, Servant, Nicolas, Piolot, Tristan, van Berkum, Nynke L., Meisig, Johannes, Sedat, John, Gribnau, Joost, Barillot, Emmanuel, Bluthgen, Nils, Dekker, Job, and Heard, Edith

Subjects
DNA -- Physiological aspects -- Research, Stem cells -- Physiological aspects -- Genetic aspects -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

In eukaryotes transcriptional regulation often involves multiple long-range elements and is influenced by the genomic environment (1). A prime example of this concerns the mouse X-inactivation centre (Xic), which orchestrates the initiation of X-chromosome inactivation (XCI) by controlling the expression of the nonprotein-coding Xist transcript. The extent of Xic sequences required for the proper regulation of Xist remains unknown. Here we use chromosome conformation capture carbon-copy (5C) (2) and super-resolution microscopy to analyse the spatial organization of a 4.5-megabases (Mb) region including Xist.We discover a series of discrete 200-kilobase to 1 Mb topologically associating domains (TADs), present both before and after cell differentiation and on the active and inactive X. TADs align with, but do not rely on, several domain-wide features of the epigenome, such as H3K27me3 or H3K9me2 blocks and lamina-associated domains. TADs also align with coordinately regulated gene clusters. Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. The Xist/Tsix sense/antisense unit illustrates how TADs enable the spatial segregation of oppositely regulated chromosomal neighbourhoods, with the respective promoters of Xist and Tsix lying in adjacent TADs, each containing their known positive regulators. We identify a novel distal regulatory region of Tsix within its TAD, which produces a long intervening RNA, Linx. In addition to uncovering a new principle of cis-regulatory architecture of mammalian chromosomes, our study sets the stage for the full genetic dissection of the X-inactivation centre., The X-inactivation centre was originally defined by deletions and translocations as a region spanning several megabases (3,4), and contains several elements known to affect Xist activity, including its repressive antisense [...]

Published
2012
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113. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression

Author

Wang, Kevin C., Yang, Yul W., Liu, Bo, Sanyal, Amartya, Corces-Zimmerman, Ryan, Chen, Yong, Lajoie, Bryan R., Protacio, Angeline, Flynn, Ryan A., Gupta, Rajnish A., Wysocka, Joanna, Lei, Ming, Dekker, Job, Helms, Jill A., and Chang, Howard Y.

Subjects
Gene expression -- Research -- Physiological aspects, Chromatin -- Physiological aspects -- Research, RNA -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The genome is extensively transcribed into long intergenic non-coding RNAs (lincRNAs), many of which are implicated in gene silencing (1,2). Potential roles of lincRNAs in gene activation are much less understood (3-5). Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control (6). Some locus control elements and enhancers transcribe lincRNAs (7-10), hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5'of the cluster (11). Here we identify HOTTIP, alincRNA transcribed from the 5' tip of the HOXA locus that coordinates the activation of several 5' HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation., We examined chromosome structure and histone modifications in human primary fibroblasts derived from several anatomic sites (12), and found distinctive differences in the HOXA locus. High throughput chromosome conformation capture [...]

Published
2011
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115. Mediator and cohesin connect gene expression and chromatin architecture

Author

Kagey, Michael H., Newman, Jamie J., Bilodeau, Steve, Zhan, Ye, Orlando, David A., van Berkum, Nynke L., Ebmeier, Christopher C., Goossens, Jesse, Rahl, Peter B., Levine, Stuart S., Taatjes, Dylan J., Dekker, Job, and Young, Richard A.

Subjects
Gene expression -- Physiological aspects -- Research, Chromatin -- Properties -- Physiological aspects -- Research, Cytogenetics -- Research -- Physiological aspects, Transcription factors -- Properties -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell., Transcription factors control the gene expression programs that establish and maintain cell state (1,2). These factors bind to enhancer elements that can be located some distance from the core promoter [...]

Published
2010
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118. The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome

Author

Gdula, Michal R, Nesterova, Tatyana B, Pintacuda, Greta, Godwin, Jonathan, Zhan, Ye, Ozadam, Hakan, McClellan, Michael, Moralli, Daniella, Krueger, Felix, Green, Catherine M, Reik, Wolf, Kriaucionis, Skirmantas, Heard, Edith, Dekker, Job, Brockdorff, Neil, University of Oxford [Oxford], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), The Wellcome Trust Centre for Human Genetics [Oxford], The Babraham Institute [Cambridge, UK], Institut Curie [Paris], Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chaire Epigénétique et mémoire cellulaire, Collège de France (CdF (institution)), Gdula, Michal R [0000-0002-8667-7359], Nesterova, Tatyana B [0000-0001-7740-4386], Pintacuda, Greta [0000-0001-5126-2279], Zhan, Ye [0000-0001-9280-1718], Moralli, Daniella [0000-0001-7977-8496], Krueger, Felix [0000-0002-5513-3324], Heard, Edith [0000-0001-8052-7117], Dekker, Job [0000-0001-5631-0698], and Apollo - University of Cambridge Repository

Subjects
Male, Transcriptional Activation, Chromosomal Proteins, Non-Histone, Science, [SDV]Life Sciences [q-bio], Polycomb-Group Proteins, Exons, DNA Methylation, Fibroblasts, Article, Cell Line, Histones, Gene Knockout Techniques, Mice, X Chromosome Inactivation, Animals, Point Mutation, CpG Islands, Female, lcsh:Q, CRISPR-Cas Systems, lcsh:Science, Alleles
Abstract

The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation of two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 mutant cells reveals the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including A/B compartments and partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred following SmcHD1 knockout in a somatic cell model, but in this case, independent of Xi gene derepression. We conclude that SmcHD1 is a key factor in defining the unique chromosome architecture of Xi., The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.

Published
2018

120. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. James, Stone, Eric A., Batzoglou, Serafim, Goldman, Nick, Hardison, Ross C., Haussler, David, Miller, Webb, Sidow, Arend, Trinklein, Nathan D., Zhang, Zhengdong D., Barrera, Leah, Stuart, Rhona, King, David C., Ameur, Adam, Enroth, Stefan, Bieda, Mark C., Kim, Jonghwan, Bhinge, Akshay A., Jiang, Nan, Liu, Jun, Yao, Fei, Vega, Vinsensius B., Lee, Charlie W.H., Ng, Patrick, Yang, Annie, Moqtaderi, Zarmik, Zhu, Zhou, Xu, Xiaoqin, Squazzo, Sharon, Oberley, Matthew J., Inman, David, Singer, Michael A., Richmond, Todd A., Munn, Kyle J., Rada-Iglesias, Alvaro, Wallerman, Ola, Komorowski, Jan, Fowler, Joanna C., Couttet, Phillippe, Bruce, Alexander W., Dovey, Oliver M., Ellis, Peter D., Langford, Cordelia F., Nix, David A., Euskirchen, Ghia, Hartman, Stephen, Urban, Alexander E., Kraus, Peter, Van Calcar, Sara, Heintzman, Nate, Hoon Kim, Tae, Wang, Kun, Qu, Chunxu, Hon, Gary, Luna, Rosa, Glass, Christopher K., Rosenfeld, M. Geoff, Aldred, Shelley Force, Cooper, Sara J., Halees, Anason, Lin, Jane M., Shulha, Hennady P., Zhang, Xiaoling, Xu, Mousheng, Haidar, Jaafar N. S., Yu, Yong, Birney*, Ewan, Iyer, Vishwanath R., Green, Roland D., Wadelius, Claes, Farnham, Peggy J., Ren, Bing, Harte, Rachel A., Hinrichs, Angie S., Trumbower, Heather, Clawson, Hiram, Hillman-Jackson, Jennifer, Zweig, Ann S., Smith, Kayla, Thakkapallayil, Archana, Barber, Galt, Kuhn, Robert M., Karolchik, Donna, Armengol, Lluis, Bird, Christine P., de Bakker, Paul I. W., Kern, Andrew D., Lopez-Bigas, Nuria, Martin, Joel D., Stranger, Barbara E., Woodroffe, Abigail, Davydov, Eugene, Dimas, Antigone, Eyras, Eduardo, Hallgrimsdottir, Ingileif B., Huppert, Julian, Zody, Michael C., Abecasis, Goncalo R., Estivill, Xavier, Bouffard, Gerard G., Guan, Xiaobin, Hansen, Nancy F., Idol, Jacquelyn R., Maduro, Valerie V.B., Maskeri, Baishali, McDowell, Jennifer C., Park, Morgan, Thomas, Pamela J., Young, Alice C., Blakesley, Robert W., Baylor College of Medicine, Human Genome Sequencing Center, Muzny, Donna M., Sodergren, Erica, Wheeler, David A., Worley, Kim C., Jiang, Huaiyang, Weinstock, George M., Gibbs, Richard A., Graves, Tina, Fulton, Robert, Mardis, Elaine R., Wilson, Richard K., Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B., Chang, Jean L., Lindblad-Toh, Kerstin, Lander, Eric S., Koriabine, Maxim, Nefedov, Mikhail, Osoegawa, Kazutoyo, Yoshinaga, Yuko, Zhu, Baoli, and de Jong, Pieter J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
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121. The genome-wide multi-layered architecture of chromosome pairing in early Drosophila embryos

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Erceg, Jelena, AlHaj Abed, Jumana, Goloborodko, Anton, Lajoie, Bryan R., Fudenberg, Geoffrey, Abdennur, Nezar Alexander, Imakaev, Maksim Viktorovich, McCole, Ruth B., Nguyen, Son C., Saylor, Wren, Joyce, Eric F., Senaratne, T. Niroshini, Hannan, Mohammed A., Nir, Guy, Dekker, Job, Mirny, Leonid A, Wu, C.-ting, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Erceg, Jelena, AlHaj Abed, Jumana, Goloborodko, Anton, Lajoie, Bryan R., Fudenberg, Geoffrey, Abdennur, Nezar Alexander, Imakaev, Maksim Viktorovich, McCole, Ruth B., Nguyen, Son C., Saylor, Wren, Joyce, Eric F., Senaratne, T. Niroshini, Hannan, Mohammed A., Nir, Guy, Dekker, Job, Mirny, Leonid A, and Wu, C.-ting

Abstract

Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focus on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first address long-standing questions regarding the structure of embryonic homolog pairing and, to this end, develop a haplotype-resolved Hi-C approach to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This computational approach, which we call Ohm, reveals pairing to be surprisingly structured genome-wide, with trans-homolog domains, compartments, and interaction peaks, many coinciding with analogous cis features. We also find a significant genome-wide correlation between pairing, transcription during zygotic genome activation, and binding of the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered a century ago in Drosophila. Finally, we demonstrate the versatility of our haplotype-resolved approach by applying it to mammalian embryos.

Published
2020

122. A pathway for mitotic chromosome formation

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, Gibcus, Johan H., Samejima, Kumiko, Goloborodko, Anton, Samejima, Itaru, Naumova, Natalia, Nubler, Johannes, Kanemaki, Masato T., Xie, Linfeng, Paulson, James R., Earnshaw, William C., Mirny, Leonid A, Dekker, Job, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, Gibcus, Johan H., Samejima, Kumiko, Goloborodko, Anton, Samejima, Itaru, Naumova, Natalia, Nubler, Johannes, Kanemaki, Masato T., Xie, Linfeng, Paulson, James R., Earnshaw, William C., Mirny, Leonid A, and Dekker, Job

Abstract

Mitotic chromosomes fold as compact arrays of chromatin loops.To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed.During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops.The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold.The size of helical turns progressively increases to ~12megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding., National Human Genome Research Institute (Grant HG003143), National Institutes of Health Common Fund (Grant DK107980)

Published
2020

123. Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, Nora, Elphège P., Goloborodko, Anton, Valton, Anne-Laure, Gibcus, Johan H., Uebersohn, Alec, Abdennur, Nezar Alexander, Dekker, Job, Mirny, Leonid A, Bruneau, Benoit G., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, Nora, Elphège P., Goloborodko, Anton, Valton, Anne-Laure, Gibcus, Johan H., Uebersohn, Alec, Abdennur, Nezar Alexander, Dekker, Job, Mirny, Leonid A, and Bruneau, Benoit G.

Abstract

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Furthermore, our data support that CTCF mediates transcriptional insulator function through enhancer blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding, these results provide new fundamental insights into the rules governing mammalian genome organization., National Human Genome Research Institute (Grants R01 HG003143, U54 HG007010 and U01 HG007910), National Cancer Institute (Grant U54 CA193419), National Institutes of Health (Grants U54 DK107980, U01 DA040588), National Institute of General Medical Sciences (Grant R01 GM112720), National Institute of Allergy and Infectious Diseases (Grant U01 R01AI117839)

Published
2020

124. Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Finn, Elizabeth H., Pegoraro, Gianluca, Brandão, Hugo B., Valton, Anne-Laure, Oomen, Marlies E., Dekker, Job, Mirny, Leonid A, Misteli, Tom, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Finn, Elizabeth H., Pegoraro, Gianluca, Brandão, Hugo B., Valton, Anne-Laure, Oomen, Marlies E., Dekker, Job, Mirny, Leonid A, and Misteli, Tom

Abstract

Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population. High-throughput imaging of several hundred chromatin interactions in individual cells reveals extensive heterogenity in spatial genome organization at the single-cell level., NIH (Grant U54 DK107890)

Published
2020

125. Highly structured homolog pairing reflects functional organization of the Drosophila genome

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, AlHaj Abed, Jumana, Erceg, Jelena, Goloborodko, Anton, Nguyen, Son C., McCole, Ruth B., Saylor, Wren, Fudenberg, Geoffrey, Lajoie, Bryan R., Dekker, Job, Mirny, Leonid A., Wu, C.-ting, Goloborodko, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Physics, AlHaj Abed, Jumana, Erceg, Jelena, Goloborodko, Anton, Nguyen, Son C., McCole, Ruth B., Saylor, Wren, Fudenberg, Geoffrey, Lajoie, Bryan R., Dekker, Job, Mirny, Leonid A., Wu, C.-ting, and Goloborodko

Abstract

Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional implication genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing, including the disruption of some interaction peaks. Keywords: Computational biology and bioinformatics; Epigenetics; Functional genomics; Molecular biology, National Institute of General Medical Sciences (U.S.) (Grant R01HD091797), National Institute of General Medical Sciences (U.S.) (Grant R01GM123289), National Institute of General Medical Sciences (U.S.) (Grant DP1GM106412), National Institute of General Medical Sciences (U.S.) (Grant R01 GM114190)

Published
2020

127. Preface

Author

Walhout, A.J. Marian, primary, Vidal, Marc, additional, and Dekker, Job, additional

Published
2013
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128. List of Contributors

Author

Albert, Réka, primary, Andrews, Brenda, additional, Bader, Gary D., additional, Ballance, Heather, additional, Barabási, Albert-László, additional, Barzel, Baruch, additional, Baryshnikova, Anastasia, additional, Bastiaens, Philippe I.H., additional, Benfey, Philip N., additional, Boone, Charles, additional, Brogaard, Kristin R., additional, Bulyk, Martha L., additional, Calderwood, Michael A., additional, Carvunis, Anne-Ruxandra, additional, Castrillo, Juan I., additional, Costanzo, Michael, additional, Cox, Jürgen, additional, Cusick, Michael E., additional, Davidson, Eric H., additional, Davis, Mark M., additional, Dekker, Job, additional, Flores, Mauricio A., additional, Fraser, Andrew, additional, Giaever, Guri, additional, Gonçalves, Bruno, additional, Grecco, Hernán E., additional, Guigó, Roderic, additional, Hefzi, Hooman, additional, Hein, Marco Y., additional, Hogenesch, John B., additional, Hood, Leroy, additional, Iyengar, Ravi, additional, Kitano, Hiroaki, additional, Kulkarni, Meghana M., additional, Lee, Anna Y., additional, Lehner, Ben, additional, Lemischka, Ihor, additional, Lewis, Nathan E., additional, Ma'ayan, Avi, additional, Mann, Matthias, additional, Mariottini, Chiara, additional, Myers, Chad L., additional, Nislow, Corey, additional, Novák, Béla, additional, Oliver, Stephen G., additional, Palsson, Bernhard O., additional, Papatsenko, Dmitri, additional, Peter, Isabelle S., additional, Perra, Nicola, additional, Perrimon, Norbert, additional, Pir, Pinar, additional, Price, Nathan D., additional, Roth, Frederick P., additional, Savageau, Michael A., additional, Schadt, Eric E., additional, Scheres, Ben, additional, Schmick, Malte, additional, Sharma, Amitabh, additional, Sharma, Kirti, additional, Shen-Orr, Shai S., additional, Sun, Zhongyao, additional, Superti-Furga, Giulio, additional, Tyson, John J., additional, VanderSluis, Benjamin, additional, van Steensel, Bas, additional, Venkataraman, Anand, additional, Vespignani, Alessandro, additional, Vidal, Marc, additional, Wagner, Andreas, additional, Walhout, A.J. Marian, additional, and Xu, Huilei, additional

Published
2013
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129. Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML

Author

Tothova, Zuzana, primary, Valton, Anne-Laure, additional, Gorelov, Rebecca A., additional, Vallurupalli, Mounica, additional, Krill-Burger, John M., additional, Holmes, Amie, additional, Landers, Catherine C., additional, Haydu, J. Erika, additional, Malolepsza, Edyta, additional, Hartigan, Christina, additional, Donahue, Melanie, additional, Popova, Katerina D., additional, Koochaki, Sebastian, additional, Venev, Sergey V., additional, Rivera, Jeanne, additional, Chen, Edwin, additional, Lage, Kasper, additional, Schenone, Monica, additional, D’Andrea, Alan D., additional, Carr, Steven A., additional, Morgan, Elizabeth A., additional, Dekker, Job, additional, and Ebert, Benjamin L., additional

Published
2021
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130. Cohesin-mediated loop anchors confine the location of human replication origins

Author

Emerson, Daniel, primary, Zhao, Peiyao A, additional, Klein, Kyle, additional, Ge, Chunmin, additional, Zhou, Linda, additional, Sasaki, Takayo, additional, Yang, Liyan, additional, Venvev, Sergey V., additional, Gibcus, Johan H., additional, Dekker, Job, additional, Gilbert, David M., additional, and Phillips-Cremins, Jennifer E., additional

Published
2021
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131. Systematic evaluation of chromosome conformation capture assays

Author

Oksuz, Betul Akgol, primary, Yang, Liyan, additional, Abraham, Sameer, additional, Venev, Sergey V., additional, Krietenstein, Nils, additional, Parsi, Krishna Mohan, additional, Ozadam, Hakan, additional, Oomen, Marlies E., additional, Nand, Ankita, additional, Mao, Hui, additional, Genga, Ryan MJ, additional, Maehr, Rene, additional, Rando, Oliver J., additional, Mirny, Leonid A., additional, Gibcus, Johan Harmen, additional, and Dekker, Job, additional

Published
2020
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137. A closer look at long-range chromosomal interactions

Author

Dekker, Job

Subjects
Chromatin -- Research, Chromosomes -- Research, Biological sciences, Chemistry
Abstract

Higher-order chromosome organization is emerging as a major determinant of gene regulation. Although the structure of chromatin at the level of individual nucleosomes has been studied in considerable detail, less is known about higher levels of organization. Two new methods have been developed that can be used to obtain detailed information about the higher-order folding of chromatin. Using these methods, long-range looping interactions have been shown to occur upon activation of the murine [beta]-globin locus, explaining the long-standing question of how gene regulatory elements can act at large genomic distances from their target genes.

Published
2003

139. Capturing chromosome conformation. (Reports)

Author

Dekker, Job, Rippe, Karsten, Dekker, Martijn, and Kleckner, Nancy

Subjects
DNA -- Research, Heredity -- Research, Chromosomes -- Research, Science and technology, Research
Abstract

We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the [G.sub.1] stage of the ceil cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring., Important chromosomal activities have been linked with both structural properties and spatial conformations of chromosomes. Local properties of the chromatin fiber influence gene expression, origin firing, and DNA repair [e.g., [...]

Published
2002

149. Spatial organization of transcribed eukaryotic genes

Author

Leidescher, Susanne, primary, Ribisel, Johannes, additional, Ullrich, Simon, additional, Feodorova, Yana, additional, Hildebrand, Erica, additional, Bultmann, Sebastian, additional, Link, Stephanie, additional, Thanisch, Katharina, additional, Mulholland, Christopher, additional, Dekker, Job, additional, Leonhardt, Heinrich, additional, Mirny, Leonid, additional, and Solovei, Irina, additional

Published
2020
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150. Ultrastructural Details of Mammalian Chromosome Architecture

Author

Krietenstein, Nils, primary, Abraham, Sameer, additional, Venev, Sergey V., additional, Abdennur, Nezar, additional, Gibcus, Johan, additional, Hsieh, Tsung-Han S., additional, Parsi, Krishna Mohan, additional, Yang, Liyan, additional, Maehr, René, additional, Mirny, Leonid A., additional, Dekker, Job, additional, and Rando, Oliver J., additional

Published
2020
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