Follicle stimulating hormone stimulates farnesyl-diphosphate farnesyltransferase 1 expression through LSD1Ser54p in chicken ovarian granulosa cells

Ovarian follicular development in laying hens is tightly regulated by a variety of endocrine and cellular factors, among which follicle-stimulating hormone (FSH) plays a decisive role. Our previous study demonstrated that phosphorylation of LSD1 at serine 54 (LSD1Ser54p) level increases after follicle selection, and FSH induces LSD1Ser54p in chicken hierarchical follicular granulosa cells (Post-GCs), suggesting a critical role of LSD1Ser54p in chicken follicle selection. To elucidate the underlying mechanism, we first determined the expression pattern of LSD1Ser54p in follicular tissues and confirmed its role in reducing the levels of H3K4me1/2 and H3K9me1/2 in Post-GCs. By integrating transcriptome sequencing and CUT&Tag chromatin analysis, we identified genes that are targeted by FSH and directly bound by LSD1Ser54p, with farnesyl-diphosphate farnesyltransferase 1 (FDFT1) being selected for further investigations. In depth analysis of the histone modification status at the FDFT1 promoter revealed that LSD1Ser54p specifically removes H3K9me1/2 methylation, thereby alleviating chromatin repression and activating FDFT1 transcription, which ultimately promotes the cholesterol synthesis. Our findings reveal an epigenetic regulatory pathway-the FSH-LSD1Ser54p-H3K9me1/2-FDFT1 axis-operating during chicken follicle selection, providing new molecular insights into avian reproductive physiology.