当前位置: X-MOL 学术Mol. Cell. Endocrinol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-11-21 , DOI: 10.1016/j.mce.2020.111085
Isao Tamura 1 , Ryo Maekawa 1 , Kosuke Jozaki 2 , Yasuyuki Ohkawa 3 , Haruka Takagi 1 , Yumiko Doi-Tanaka 1 , Yuichiro Shirafuta 1 , Yumiko Mihara 1 , Toshiaki Taketani 1 , Shun Sato 1 , Hiroshi Tamura 1 , Norihiro Sugino 1
Affiliation  

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.



中文翻译:

转录因子C /EBPβ诱导的全基因组H3K27ac和人子宫内膜间质细胞的蜕膜中上调的基因表达

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。

更新日期:2020-11-22
down
wechat
bug