Open AccessFoxa2 and H2A.Z Mediate Nucleosome Depletion during Embryonic Stem Cell Differentiation
Author(s) -
Zhaoyu Li,
Paul Gadue,
Kaifu Chen,
Yang Jiao,
Geetu Tuteja,
Jonathan Schug,
Wei Li,
Klaus H. Kaestner
Publication year - 2012
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2012.11.018
Subject(s) - nucleosome , biology , chromatin , histone , microbiology and biotechnology , cellular differentiation , histone methylation , epigenetics , chromatin remodeling , swi/snf , genetics , foxa2 , histone code , embryonic stem cell , dna methylation , gene expression , gene
Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression. Nucleosome depletion during ES cell differentiation is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes. Thus, both epigenetic and genetic regulators cooperate to control nucleosome dynamics during ES cell fate decisions.
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