Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation

Yuan Gao, Haiyun Gan, Zhenkun Lou, Zhiguo Zhang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in ES cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation. Mechanistically, the Asf1a–histone interaction, but not the role of Asf1a in nucleosome assembly, is required for gene transcription. Asf1a is recruited to several bivalent promoters, partially through association with transcription factors, and mediates nucleosome disassembly during differentiation. We suggest that Asf1a-mediated nucleosome disassembly provides a means for resolution of bivalent domain barriers for induction of lineage-specific genes during differentiation.

Original languageEnglish (US)
Pages (from-to)E6162-E6171
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number27
DOIs
StatePublished - Jul 3 2018

Keywords

  • Bivalent chromatin domain
  • Embryonic stem cell differentiation
  • Histone chaperone
  • Nucleosome disassembly

ASJC Scopus subject areas

  • General

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