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Cell. 2014 Oct 9;159(2):374-87. doi: 10.1016/j.cell.2014.09.030.

Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.

Author information

1
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
2
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Systems Biology Center, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P.R. China, 712100.
4
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Systems Biology Center, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: zhaok@nhlbi.nih.gov.
6
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.

Abstract

The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.

PMID:
25303531
PMCID:
PMC4197132
DOI:
10.1016/j.cell.2014.09.030
[Indexed for MEDLINE]
Free PMC Article
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