Transcription factor 21 regulates expression of ERβ and SF-1 via upstream stimulatory factor-2 in endometriotic tissues

Publication date: Available online 7 July 2018Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Pei-Li Wu, Yan Zhou, Cheng Zeng, Xin Li, Zhao-Tong Dong, Ying-Fang Zhou, Serdar E. Bulun, Qing XueAbstractSteroidogenic factor-1 (SF-1, encoded by NR5A1) and estrogen receptor beta (ERβ, encoded by ESR2), which are highly expressed in endometriotic stromal cells (ESCs), contribute to the pathogenesis of endometriosis, but the regulation mechanism remains largely unknown. Transcription factor 21 (TCF21) belongs to the helix-loop-helix (bHLH) family characterized by regulating gene expression via binding to E-box element. Here, we attempted to determine the molecular mechanism of TCF21 on SF-1 and ERβ expression in endometriosis. We found that TCF21 expression in ESCs was higher than that in endometrial stromal cells (EMs), and positively correlated with SF-1 and ERβ expression in ESCs. Since the importance of E-box element for NR5A1 promoter activity has been previously reported, we performed site-mutation and luciferase assay, revealing that the E-box sequence in the ESR2 promoter is also a critical element modulating ERβ expression. Upstream stimulatory factor 2 (USF2) is another bHLH factor implicated in transcriptional regulation. Further analyses elucidated that it is not TCF21, but USF2 exhibited higher binding affinities in ESCs to NR5A1 and ESR2 promoters than in EMs. Additionally, TCF21 knockdown significantly decreased the binding activ...

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - July 10, 2018 Category: Genetics & Stem Cells Source Type: research