3D Chromosome Regulatory Landscape of Human Pluripotent Cells

In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET...

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Main Authors: Ji, Xiong, Powell, Benjamin E., Shachar, Sigal, Hnisz, Denes, Pegoraro, Gianluca, Lee, Tong Ihn, Misteli, Tom, Dadon, Daniel Benjamin, Fan, Zi Peng, Borges-Rivera, Diego Ramon, Weintraub, Abraham Selby, Jaenisch, Rudolf, Young, Richard A.
Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/107115
https://orcid.org/0000-0002-7256-3158
https://orcid.org/0000-0002-1650-2289
https://orcid.org/0000-0003-0998-9882
https://orcid.org/0000-0001-8855-8647
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author Ji, Xiong
Powell, Benjamin E.
Shachar, Sigal
Hnisz, Denes
Pegoraro, Gianluca
Lee, Tong Ihn
Misteli, Tom
Dadon, Daniel Benjamin
Fan, Zi Peng
Borges-Rivera, Diego Ramon
Weintraub, Abraham Selby
Jaenisch, Rudolf
Young, Richard A.
author2 Massachusetts Institute of Technology. Computational and Systems Biology Program
author_facet Massachusetts Institute of Technology. Computational and Systems Biology Program
Ji, Xiong
Powell, Benjamin E.
Shachar, Sigal
Hnisz, Denes
Pegoraro, Gianluca
Lee, Tong Ihn
Misteli, Tom
Dadon, Daniel Benjamin
Fan, Zi Peng
Borges-Rivera, Diego Ramon
Weintraub, Abraham Selby
Jaenisch, Rudolf
Young, Richard A.
author_sort Ji, Xiong
collection MIT
description In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
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spelling mit-1721.1/1071152022-09-23T10:20:51Z 3D Chromosome Regulatory Landscape of Human Pluripotent Cells Ji, Xiong Powell, Benjamin E. Shachar, Sigal Hnisz, Denes Pegoraro, Gianluca Lee, Tong Ihn Misteli, Tom Dadon, Daniel Benjamin Fan, Zi Peng Borges-Rivera, Diego Ramon Weintraub, Abraham Selby Jaenisch, Rudolf Young, Richard A. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Dadon, Daniel Benjamin Fan, Zi Peng Borges-Rivera, Diego Ramon Weintraub, Abraham Selby Jaenisch, Rudolf Young, Richard A In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease. Center for Cancer Research (National Cancer Institute (U.S.)) National Institutes of Health (U.S.). Intramural Research Program Virginia and Daniel K. Ludwig Graduate Fellowship National Institutes of Health (U.S.) (Grants HG002668 and HD 045022) Simons Foundation (Grant SFLIFE 286977) 2017-02-23T15:24:41Z 2017-02-23T15:24:41Z 2015-12 2015-10 Article http://purl.org/eprint/type/JournalArticle 1934-5909 http://hdl.handle.net/1721.1/107115 Ji, Xiong et al. “3D Chromosome Regulatory Landscape of Human Pluripotent Cells.” Cell Stem Cell 18.2 (2016): 262–275. https://orcid.org/0000-0002-7256-3158 https://orcid.org/0000-0002-1650-2289 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.stem.2015.11.007 Cell Stem Cell Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier PMC
spellingShingle Ji, Xiong
Powell, Benjamin E.
Shachar, Sigal
Hnisz, Denes
Pegoraro, Gianluca
Lee, Tong Ihn
Misteli, Tom
Dadon, Daniel Benjamin
Fan, Zi Peng
Borges-Rivera, Diego Ramon
Weintraub, Abraham Selby
Jaenisch, Rudolf
Young, Richard A.
3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title_full 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title_fullStr 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title_full_unstemmed 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title_short 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
title_sort 3d chromosome regulatory landscape of human pluripotent cells
url http://hdl.handle.net/1721.1/107115
https://orcid.org/0000-0002-7256-3158
https://orcid.org/0000-0002-1650-2289
https://orcid.org/0000-0003-0998-9882
https://orcid.org/0000-0001-8855-8647
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