3D Chromosome Regulatory Landscape of Human Pluripotent Cells
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3D regulatory.pdf
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1.38 MB
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Author(s)
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
Date Issued
December 2015
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Ji, Xiong et al. “3D Chromosome Regulatory Landscape of Human Pluripotent Cells.” Cell Stem Cell 18.2 (2016): 262–275.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1016/j.stem.2015.11.007
