Importance of C/EBPβ binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL, and Mn-SOD by cAMP in human endometrial stromal cells.
Importance of C/EBPβ binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL, and Mn-SOD by cAMP in human endometrial stromal cells.
复制标题
DOI：
10.1210/en.2013-1569
复制
发表时间：
2014
期刊：
影响因子：
4.8
通讯作者：
I. Tamura;Shun Sato;Maki Okada;M. Tanabe;L. Lee;R. Maekawa;H. Asada;Y. Yamagata;H. Tamura;N. Sugino
中科院分区：
文献类型：
--
作者：
I. Tamura;Shun Sato;Maki Okada;M. Tanabe;L. Lee;R. Maekawa;H. Asada;Y. Yamagata;H. Tamura;N. Sugino
在决策过程中，基因表达的动态变化发生在人类的子宫基质细胞（ESC）中。了解表观遗传机制的作用，例如组蛋白在与决策相关的基因调节中的作用。上调IGF结合蛋白-1（IGFBP-1），催乳素（PRL）和锰超氧化物歧化酶（MN-SOD）在ESC中的表达通过实时RT-PCR确定-1，PRL和MN-SOD mRNA表达式。通过染色质免疫沉淀测定法检查了启动子中的[H3K27AC]），使用小的干扰RNA方法进行了C/EBPβ的敲低。启动子中的H3K27AC水平。 CAMP在增强子区域中增加了MN-SOD mRNA水平和C/EBPβ的结合活性。 C/EBPβ敲低抑制。他们的启动子但对决定性化过程中人类ESC中的Mn-SOD基因表达有所不同。
Dynamic changes of gene expressions occur in human endometrial stromal cells (ESCs) during decidualization. CCAAT/enhancer-binding proteinβ (C/EBPβ) regulates the expression of a number of decidualization-related genes. In addition to transcription factors, it is important to know the role of epigenetic mechanisms, such as histone modifications in the regulation of decidualization-related genes. This study investigated the molecular and epigenetic mechanisms by which cAMP up-regulates the expression of IGF-binding protein-1 (IGFBP-1), prolactin (PRL), and manganese superoxide dismutase (Mn-SOD) in ESC. ESCs isolated from proliferative phase endometrium were incubated with cAMP to induce decidualization. IGFBP-1, PRL, and Mn-SOD mRNA expressions were determined by real-time RT-PCR. The C/EBPβ binding and histone modification status (acetylation of histone-H3 lysine-27 [H3K27ac]) in the promoter were examined by chromatin immunoprecipitation assay. Knockdowns of C/EBPβ were performed using the small interfering RNA method. cAMP induced mRNA expressions of IGFBP-1 and PRL accompanied by the increases in both C/EBPβ binding activities and H3K27ac levels in the promoters. The stimulatory effects of cAMP on mRNA levels and H3K27ac levels were completely abolished by C/EBPβ knockdown. cAMP increased Mn-SOD mRNA levels and C/EBPβ binding activities in the enhancer region. C/EBPβ knockdown inhibited Mn-SOD mRNA levels. The H3K27ac levels in the enhancer were high before cAMP stimulus but were not further increased by cAMP and were not inhibited by C/EBPβ knockdown. These results show that C/EBPβ regulates the expression of IGFBP-1 and PRL by altering the histone acetylation status of their promoters but differently regulates Mn-SOD gene expression in human ESC during decidualization.