期刊
CELL SYSTEMS
卷 7, 期 5, 页码 482-+出版社
CELL PRESS
DOI: 10.1016/j.cels.2018.09.003
关键词
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资金
- EMBL
- US National Institutes of Health (NIH) through the 4D Nucleome (4DN) common fund [U01 EB021223, U01 DA047728]
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M004023/1, BB/G015678/1]
- Wellcome Trust
- UK Medical Research Council (MRC) [203151/Z/16/Z, 097922/Z/11/Z]
- European Commission Seventh Framework Programme (FP7) through the collaborative research project RADIANT [305626]
- EMBL Interdisciplinary Postdoc (EIPOD) fellowship under Marie Curie Actions COFUND
- EMBL International PhD Programme (EIPP)
- BBSRC [BB/G015678/1, BB/M004023/1] Funding Source: UKRI
The genome of pluripotent stem cells adopts a unique three-dimensional architecture featuring weakly condensed heterochromatin and large nucleo-some-free regions. Yet, it is unknown whether structural loops and contact domains display characteristics that distinguish embryonic stem cells (ESCs) from differentiated cell types. We used genome-wide chromosome conformation capture and super-resolution imaging to determine nuclear organization in mouse ESC and neural stem cell (NSC) derivatives. We found that loss of pluripotency is accompanied by widespread gain of structural loops. This general architectural change correlates with enhanced binding of CTCF and cohesins and more pronounced insulation of contacts across chromatin boundaries in lineage-committed cells. Reprogramming NSCs to pluripotency restores the unique features of ESC domain topology. Domains defined by the anchors of loops established upon differentiation are enriched for developmental genes. Chromatin loop formation is a pervasive structural alteration to the genome that accompanies exit from pluripotency and delineates the spatial segregation of developmentally regulated genes.
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