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 4,190 genes that were upregulated by cAMP, C/EBPβ knockdown inhibited these upregulation in 2,239 genes (53.4%), indicating that they are under the regulation of C/EBPβ. cAMP increased H3K27ac in 1,272 of the 2,239 genes. C/EBPβ knockdown abolished the increase of H3K27ac in almost all genes (1,263 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.

我们以前报道，在整个基因组H3K27乙酰化（H3K27ac）能提高人的子宫内膜间质细胞（ESC）蜕膜化过程中。然而，它的机制还没有得到澄清。我们还报道说，C /EBPβ充当先锋因素引发染色质增加IGFBP-1和PRL推动者H3K27ac重塑。因此，C /EBPβ可能参与蜕膜期间H3K27ac的全基因组的增加。在这项研究中，我们研究了C /EBPβ是否会导致全基因组H3K27ac修改和蜕膜化过程中调节基因的表达。的cAMP用于诱导蜕膜。产生了三种类型的细胞（对照细胞、cAMP 处理的细胞和 cAMP 处理的 + C/EBPβ 敲低细胞）。即通过cAMP的上调4190个基因的，C /EBPβ敲低抑制在2239个基因（53这些上调。4％），这表明它们是C /EBPβ的调控下。环腺苷酸的2239个基因1,272增加H3K27ac。C /EBPβ击倒废除H3K27ac在几乎所有的基因（1263个基因，99.3％）的增加，这表明C /EBPβ可以通过增加H3K27ac上调基因表达。为了研究C /EBPβ如何调节H3K27ac整个基因组，我们测试的假设，即C /EBPβ结合其结合区域和人员的辅因子与组蛋白乙酰化酶的活动。为此，我们将 ChIP 序列数据与转录因子的公共 ChIP 序列数据库进行了比较，发现 p300 是最有可能与 C/EBPβ 结合到 H3K27ac 增加区域的辅因子。几个基因芯片-qPCR的证实，C /EBPβ结合靶区域，募集P300，并且增加H3K27ac。