Robert Nicholas M, Miyamoto Yoko, Taniguchi Hiroaki, Viger Robert S
Ontogeny-Reproduction Research Unit, CHUL Research Centre (CHUQ), Québec City, Que, Canada.
Mol Cell Endocrinol. 2006 Sep 26;257-258:65-74. doi: 10.1016/j.mce.2006.06.011. Epub 2006 Aug 8.
Inhibin alpha is the common subunit of the dimeric inhibin proteins known for their role in suppressing pituitary FSH secretion. In this study, we have examined the role of GATA factors and the nuclear receptor, LRH-1/NR5A2, in the regulation of inhibin alpha-subunit promoter activity. The inhibin alpha promoter contains two GATA-binding motifs that can be activated by GATA4 or GATA6. The GATA-dependence of the promoter was demonstrated by downregulating GATA expression in MA-10 cells using siRNA technology. We next examined whether GATA factors could cooperate with LRH-1, a factor recently proposed to be an important regulator of inhibin alpha-subunit transcription. Both GATA4 and GATA6 strongly synergized with LRH-1. Consistent with the cAMP-dependence of the inhibin alpha-subunit promoter, GATA/LRH-1 synergism was markedly enhanced by PKA and the co-activator protein CBP. Thus, our results identify LRH-1 as a new transcriptional partner for GATA factors in the regulation of inhibin alpha-subunit gene expression.
抑制素α是二聚体抑制素蛋白的共同亚基，以其在抑制垂体促卵泡激素（FSH）分泌中的作用而闻名。在本研究中，我们研究了GATA因子和核受体LRH-1/NR5A2在抑制素α亚基启动子活性调节中的作用。抑制素α启动子包含两个可被GATA4或GATA6激活的GATA结合基序。通过使用小干扰RNA（siRNA）技术下调MA-10细胞中的GATA表达，证明了启动子对GATA的依赖性。接下来，我们研究了GATA因子是否能与LRH-1协同作用，LRH-1是最近被认为是抑制素α亚基转录重要调节因子的一个因子。GATA4和GATA6都与LRH-1强烈协同作用。与抑制素α亚基启动子的cAMP依赖性一致，PKA和共激活蛋白CBP显著增强了GATA/LRH-1的协同作用。因此，我们的结果确定LRH-1是GATA因子在调节抑制素α亚基基因表达中的一个新的转录伙伴。
