Histone H4 hyperacetylation but not DNA methylation regulates the expression of decidualization-associated genes...

The efficiency of endometrial stromal cells (ESC) decidualization is a critical player in successful embryo implantation and further pregnancy development. Epigenetic mechanisms strictly regulate massive changes that affect endometrium in each cycle, so investigating epigenetic patterns could help identify endometrial targets for infertility treatment solutions. The aim of our study was to analyze the changes in epigenetic modulators, histone modifications, and DNA methylation during induced human ESC in vitro decidualization. Decidualization markers and epigenetic factors' gene and protein expression levels were assessed during ESC cells in vitro decidualization, performing RT-qPCR and immunoblot tests. Furthermore, chromatin immunoprecipitation (ChIP) and methylated DNA immunoprecipitation (MeDIP) analysis by the following qPCR were conducted to evaluate the level of H4hyperAc and 5-methylcytosine in the decidualization-associated gene promoter and exon regions accordingly. Our results revealed that ESC decidualization caused the down-regulation of HDAC2 and subunits of PRC2. We observed the increased global level of H4hyperAc and H3K27me3. We also demonstrated that H4hyperAc was specifically enriched in the decidualization-associated genes (WNT4, HAND2, STAT5A) promoter regions during ESC decidualization. In contrast, the DNA methylation level in these promoter regions was relatively low before ESC induction and did not vary through ESC decidualization. Our findings demonstrate that specific gene promoters' histone acetylation increases during the induced ESC decidualization, which indicates the importance of epigenetic regulation in endometrial decidualization.