Literature DB >> 26637943

Dynamic Reorganization of Extremely Long-Range Promoter-Promoter Interactions between Two States of Pluripotency.

Onkar Joshi1, Shuang-Yin Wang1, Tatyana Kuznetsova1, Yaser Atlasi1, Tianran Peng1, Pierre J Fabre2, Ehsan Habibi1, Jani Shaik1, Sadia Saeed1, Lusy Handoko1, Todd Richmond3, Mikhail Spivakov4, Daniel Burgess3, Hendrik G Stunnenberg5.   

Abstract

Serum-to-2i interconversion of mouse embryonic stem cells (mESCs) is a valuable in vitro model for early embryonic development. To assess whether 3D chromatin organization changes during this transition, we established Capture Hi-C with target-sequence enrichment of DNase I hypersensitive sites. We detected extremely long-range intra- and inter-chromosomal interactions between a small subset of H3K27me3 marked bivalent promoters involving the Hox clusters in serum-grown cells. Notably, these promoter-mediated interactions are not present in 2i ground-state pluripotent mESCs but appear upon their further development into primed-like serum mESCs. Reverting serum mESCs to ground-state 2i mESCs removes these promoter-promoter interactions in a spatiotemporal manner. H3K27me3, which is largely absent at bivalent promoters in ground-state 2i mESCs, is necessary, but not sufficient, to establish these interactions, as confirmed by Capture Hi-C on Eed(-/-) serum mESCs. Our results implicate H3K27me3 and PRC2 as critical players in chromatin alteration during priming of ESCs for differentiation.
Copyright © 2015 Elsevier Inc. All rights reserved.

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Year:  2015        PMID: 26637943     DOI: 10.1016/j.stem.2015.11.010

Source DB:  PubMed          Journal:  Cell Stem Cell        ISSN: 1875-9777            Impact factor:   24.633


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