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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Bibliographic Details
Published in:Cell stem cell 2016-02, Vol.18 (2), p.262-275
Main Authors: Ji, Xiong, Dadon, Daniel B., Powell, Benjamin E., Fan, Zi Peng, Borges-Rivera, Diego, Shachar, Sigal, Weintraub, Abraham S., Hnisz, Denes, Pegoraro, Gianluca, Lee, Tong Ihn, Misteli, Tom, Jaenisch, Rudolf, Young, Richard A.
Format: Article
Language:English
Subjects:
CCCTC-Binding Factor
Cell Cycle Proteins - metabolism
Cell Line
Chromatin - metabolism
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes, Human - genetics
Cohesins
Disease - genetics
DNA - chemistry
DNA - metabolism
Enhancer Elements, Genetic
Gene Expression Regulation
Human Embryonic Stem Cells - metabolism
Humans
Insulator Elements - genetics
MicroRNAs - metabolism
Nucleic Acid Conformation
Pluripotent Stem Cells - metabolism
Repressor Proteins
Transcription Factors - metabolism
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Summary: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. [Display omitted] •ChIA-PET analysis maps enhancers and insulators into looped domains•Cohesin-associated loops organize topologically associating domains (TADs)•Regulatory changes during cell state transitions take place within TADs•The conserved anchors of CTCF-CTCF loops are frequently mutated in cancer Ji et al. map the chromosome organizational structures that underlie gene regulation in human naive and primed pluripotent cells. Their framework of cohesin-associated CTCF loops, and the cohesin-associated enhancer-promoter loops within them, provides a reference map for future interrogation of regulatory interactions.
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2015.11.007