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

Onkar Joshi, Shuang Yin Wang, Tatyana Kuznetsova, Yaser Atlasi, Tianran Peng, Pierre J. Fabre, Ehsan Habibi, Jani Shaik, Sadia Saeed, Lusy Handoko, Todd Richmond, Mikhail Spivakov, Daniel Burgess, Hendrik G. Stunnenberg

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)748-757
Number of pages10
JournalCell Stem Cell
Volume17
Issue number6
DOIs
Publication statusPublished - 3 Dec 2015
Externally publishedYes

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