Hassan Amani, Bagu Edward T, Levesque Mathieu, Patten Shunmoogum A, Benhadjeba Samira, Edjekouane Lydia, Villemure Isabelle, Tremblay André, Moldovan Florina
CHU Sainte Justine Research Center, Montréal H3T 1C5, Canada.
Department of Basic Biomedical Sciences, Sanford Medical School, University of South Dakota, Vermillion, SD 57069, USA.
Biol Open. 2019 Jan 14;8(1):bio037390. doi: 10.1242/bio.037390.
The physiological role and the regulation of ADGRG7 are not yet elucidated. The functional involvement of this receptor was linked with different physiological process such as reduced body weight, gastrointestinal function and recently, a gene variant in ADGRG7 was observed in patients with adolescent idiopathic scoliosis. Here, we identify the as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. promoter studies indicate the presence of an ERα response half site in close vicinity of a specificity protein 1 (SP1) binding site. Mutation of the SP1 site completely abrogated the response to E2, indicating its essential requirement. ChIP confirmed the binding of SP1 and ERα to the promoter. Our results identify the gene as an estrogen-responsive gene under the control of ERα and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of This article has an associated First Person interview with the first author of the paper.
ADGRG7的生理作用及其调节机制尚未阐明。该受体的功能参与与不同的生理过程有关,如体重减轻、胃肠功能,最近还在青少年特发性脊柱侧凸患者中观察到ADGRG7的一个基因变异。在此,我们确定其为雌激素反应基因,受脊柱侧凸成骨细胞和其他细胞系中雌激素受体ERα的调控。我们发现,在青少年特发性脊柱侧凸(AIS)细胞中,其表达会因雌激素(E2)而上调。启动子研究表明,在特异性蛋白1(SP1)结合位点附近存在一个ERα反应半位点。SP1位点的突变完全消除了对E2的反应,表明其必不可少。染色质免疫沉淀(ChIP)证实了SP1和ERα与启动子的结合。我们的结果确定该基因为受ERα和SP1协同作用控制的雌激素反应基因,提示雌激素在其调节中可能发挥作用。本文配有对该论文第一作者的相关第一人称访谈。