The 17β-Estradiol induced upregulation of the Adhesion G-protein coupled receptor (ADGRG7) is modulated by ESRα and SP1 complex

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 <i>ADGRG7</i> as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that <i>ADGRG7</i> expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. <i>ADGRG7</i> 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 <i>ADGRG7</i> promoter. Our results identify the <i>ADGRG7</i> 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 <i>ADGRG7</i> This article has an associated First Person interview with the first author of the paper.