Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells
Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells
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DOI：
10.1016/j.mce.2020.111085
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发表时间：
2021-01-15
影响因子：
4.1
通讯作者：
Sugino，Norihiro
中科院分区：
文献类型：
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作者：
Tamura，Isao;Maekawa，Ryo;Sugino，Norihiro
我们之前曾报道，在人子宫内膜间质细胞(ESCs)蜕膜化过程中，H3K27乙酰化(H3K27ac)在整个基因组中增加。然而，其作用机制尚不清楚。我们还报道了C/EBPβ通过增加IGFBP-1和PRL启动子的H3K27ac，作为启动染色质重塑的先导因子。因此，C/eBPβ可能参与了蜕膜形成过程中H3K27ac基因的全基因组表达增加。在这项研究中，我们研究了C/eBPβ在蜕膜化过程中是否会引起全基因组的H3K27ac修饰并调节基因表达。用cAMP诱导蜕膜形成。产生了三种类型的细胞(对照组细胞、cAMP处理细胞和cAMP处理的C/EBPsiRNA敲除细胞)。在cAMP上调的4190个基因中，C/eBPβ基因敲除抑制了2239个基因(53.4%)的上调，表明它们受C/eBPβ的调控。在2239个基因中，cAMP增加了1272个基因中的H3K27ac。C/eBPβ基因敲除后，几乎所有基因(1263个基因，99.3%)中H3K27ac的表达均消失，提示C/eBPβ可通过上调H3K27ac而上调基因表达。为了研究C/eBPβ如何在整个基因组中调节H3K27ac，我们检验了C/eBPβ与其结合区结合并招募具有组蛋白乙酰转移酶活性的辅助因子的假设。为此，我们将我们的芯片序列数据与公开的转录因子芯片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。几个基因的芯片定量聚合酶链式反应证实C/eBPβ与靶区域结合，招募p300，并增加H3K27ac。我们的全基因组分析显示，C/eBPβ通过招募p300到启动子，在整个基因组中诱导H3K27ac并上调基因表达。
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.