Down-Regulation of the Histone Methyltransferase EZH2 Contributes to the Epigenetic Programming of Decidualizing Human Endometrial Stromal Cells

摘要: Differentiation of human endometrial stromal cells (HESC) into decidual represents a highly coordinated process essential for embryo implantation. We show that decidualizing HESC down-regulate the histone methyltransferase enhancer Zeste homolog 2 (EZH2), resulting in declining levels trimethylation 3 on lysine 27 (H3K27me3) at proximal promoters key marker genes PRL and IGFBP1. Loss H3K27me3 was associated with reciprocal enrichment acetylation same residue, indicating active remodeling from repressive to transcriptionally permissive chromatin. Chromatin immunoprecipitation coupled DNA microarray analysis demonstrated decidualization triggers genome-wide changes distribution only partly overlap those observed upon EZH2 knockdown undifferentiated HESC. Gene ontology revealed gain mark response enriched promoter regions involved transcriptional regulation growth/cell proliferation, respectively. However, loss (indicating increased chromatin accessibility) occurred selective loci functionally implicated responses stimulus. In agreement, sufficient augment induction cyclic AMP progesterone signaling. Thus, EZH2-dependent activity endometrium is integral enables transition proliferative phenotype differentiation cues.