XXXX Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation.

@entity2828 @entity38612 @entity27044 @entity23423 @entity10161 @entity855
The unique chromatin signature of @entity2828 cells is fundamental to the pluripotency and differentiation of @entity2828 cells. One key feature is the poised chromatin state of master developmental genes that are transcriptionally repressed in @entity2828 cells but ready to be activated in response to differentiation signals. Poised chromatin in @entity2828 cells contains both H3 Lys-4 trimethylation (H3K4me3) and H3 Lys-27 trimethylation (H3K27me3) methylation, indicating activating and repressing potential. However, the contribution of non-covalent chromatin structure to the poised state is not well understood. To address whether remodeling of nucleosomes is important to the poised state, we characterized the function of @entity10161 , a key regulatory subunit of the @entity2828 cell @entity855 -dependent @entity27044 ( @entity27044 ) chromatin remodeling complex (esBAF). Acute deletion of @entity10161 disrupted the differentiation potential of @entity2828 cells by altering the expression timing of key developmental genes and pluripotent genes. Our genome-wide nucleosome and histone modification analyses indicated that the disruption of gene expression timing was largely due to changes of chromatin structures at poised genes, particularly those key developmental genes mediated by @entity10161 . Specifically, @entity10161 deletion caused a nucleosome occupancy increase at H3K4me3- and/or H3K27me3-associated promoters. Moreover, H3K27me3 levels and the number of bivalent promoter genes were reduced in @entity10161 KO @entity2828 cells. We revealed that @entity10161 ablation led to elevated @entity23423 but reduced @entity38612 recruitment at nucleosome occupancy-increased regions, indicating an unexpected and complicated role of @entity10161 in regulating esBAF and Polycomb repressive complex (PRC) activities. Together, our studies identified that @entity10161 mediates esBAF and PRC functions to establish the poised chromatin configuration in @entity2828 cells, which is essential for the proper differentiation of @entity2828 cells.
