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Publication : H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation.

First Author  Hu G Year  2013
Journal  Cell Stem Cell Volume  12
Issue  2 Pages  180-92
PubMed ID  23260488 Mgi Jnum  J:194943
Mgi Id  MGI:5475082 Doi  10.1016/j.stem.2012.11.003
Citation  Hu G, et al. (2013) H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation. Cell Stem Cell 12(2):180-92
abstractText  Chromatin modifications have been implicated in the self-renewal and differentiation of embryonic stem cells (ESCs). However, the function of histone variant H2A.Z in ESCs remains unclear. We show that H2A.Z is highly enriched at promoters and enhancers and is required for both efficient self-renewal and differentiation of murine ESCs. H2A.Z deposition leads to an abnormal nucleosome structure, decreased nucleosome occupancy, and increased chromatin accessibility. In self-renewing ESCs, knockdown of H2A.Z compromises OCT4 binding to its target genes and leads to decreased binding of MLL complexes to active genes and of PRC2 complex to repressed genes. During differentiation of ESCs, inhibition of H2A.Z also compromises RA-induced RARalpha binding, activation of differentiation markers, and the repression of pluripotency genes. We propose that H2A.Z mediates such contrasting activities by acting as a general facilitator that generates access for a variety of complexes, both activating and repressive.
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