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.
Bibliographical noteCopyright © 2015 Elsevier Inc. All rights reserved.
- Cell Differentiation/genetics
- Cell Nucleus/metabolism
- Cell Proliferation/genetics
- Deoxyribonuclease I/metabolism
- Embryonic Stem Cells/cytology
- Genes, Homeobox
- Homeodomain Proteins/metabolism
- Mice, Transgenic
- Pluripotent Stem Cells/cytology
- Promoter Regions, Genetic
- Protein Domains
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- School of Medicine, Dentistry and Biomedical Sciences - Vice-Chancellor Illuminate Fellow
- Patrick G Johnston Centre for Cancer Research