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Publication : Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells.

First Author  Semba Y Year  2017
Journal  Nucleic Acids Res Volume  45
Issue  15 Pages  8758-8772
PubMed ID  28549158 Mgi Jnum  J:247133
Mgi Id  MGI:5916444 Doi  10.1093/nar/gkx475
Citation  Semba Y, et al. (2017) Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells. Nucleic Acids Res 45(15):8758-8772
abstractText  Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.
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