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

148 Citations (Scopus)


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
Issue number6
Publication statusPublished - 03 Dec 2015
Externally publishedYes

Bibliographical note

Copyright © 2015 Elsevier Inc. All rights reserved.


  • Animals
  • Cell Differentiation/genetics
  • Cell Nucleus/metabolism
  • Cell Proliferation/genetics
  • Chromatin/metabolism
  • Deoxyribonuclease I/metabolism
  • Embryonic Stem Cells/cytology
  • Genes, Homeobox
  • Histones/metabolism
  • Homeodomain Proteins/metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Pluripotent Stem Cells/cytology
  • Promoter Regions, Genetic
  • Protein Domains


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