Fig. 5.

The mechanism of BMP15-induced FSHR expression through the Smad and non-Smad pathway. For the transcription factor of FSHR (USF1) to bind to the FSHR promoter region, the promoter region DNA must be structurally accessible and USF1 must be phosphorylated. Through the Smad pathway, BMP15 phosphorylates Smad 1/5/8 to epigenetically alter the DNA structure favorably for binding of USF1 to FSHR. Through the non-Smad p38 MAPK pathway, BMP15 induces the phosphorylation of USF1 necessary for binding to FSHR