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 ADGRG7 as an estrogen-responsive gene under the regulation of estrogen receptor ERalpha in scoliotic osteoblasts and other cells lines. We found that ADGRG7 expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. ADGRG7 promoter studies indicate the presence of an ERalpha 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 ERalpha to the ADGRG7 promoter. Our results identify the ADGRG7 gene as an estrogen-responsive gene under the control of ERalpha and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of ADGRG7 This article has an associated First Person interview with the first author of the paper.

Uncontrolled Keywords

Adgrg7; Ais; Adhesion G-protein coupled receptor; Estradiol (E2); Estrogen; Gpr128; Gene regulation; Osteoblasts