We previously reported that H3K27 acetylation (H3K27ac) increases throughout the genome during decidualization of human endometrial stromal cells (ESCs). However, its mechanisms have not been clarified. We also reported that C/EBPβ acts as a pioneer factor initiating chromatin remodeling by increasing H3K27ac of IGFBP-1 and PRL promoters. Therefore, C/EBPβ may be involved in the genome-wide increase of H3K27ac during decidualization. In this study, we investigated whether C/EBPβ causes genome-wide H3K27ac modifications and regulates gene expressions during decidualization. cAMP was used to induce decidualization. Three types of cells (control cells, cAMP-treated cells, and cAMP-treated + C/EBPβ-knockdowned cells by siRNA) were generated. Of 4190 genes that were upregulated by cAMP, C/EBPβ knockdown inhibited these upregulation in 2239 genes (53.4%), indicating that they are under the regulation of C/EBPβ. cAMP increased H3K27ac in 1272 of the 2239 genes. C/EBPβ knockdown abolished the increase of H3K27ac in almost all genes (1263 genes, 99.3%), suggesting that C/EBPβ can upregulate gene expression by increasing H3K27ac. To investigate how C/EBPβ regulates H3K27ac throughout the genome, we tested the hypothesis that C/EBPβ binds to its binding regions and recruits cofactors with histone acetyltransferase activities. To do this, we collated our ChIP-sequence data with public ChIP-sequence database of transcription factors, and found that p300 is the most likely cofactor that binds to the H3K27ac-increased-regions with C/EBPβ. ChIP-qPCR of several genes confirmed that C/EBPβ binds to the target regions, recruits p300, and increases H3K27ac. Our genome-wide analysis revealed that C/EBPβ induces H3K27ac throughout the genome and upregulates gene expressions during decidualization by recruiting p300 to the promoters.
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