GSE119508
The ovulatory signal precipitates LRH-1 transcriptional switching mediated by differential chromatin accessibility.
In the ovary, follicular growth and maturation are complicated processes that involve a series of morphological and physiological changes in oocytes and somatic cells leading to ovulation and luteinization, essential processes for fertility in females. Given the complexity of ovulation, characterization of genome-wide regulatory elements is essential to understand the mechanisms governing the expression of specific genes in the rapidly differentiating follicle. We therefore employed a systems biology approach to determine global transcriptional mechanisms during the early stages of the ovulatory process. We demonstrate that, following the hormonal signal that initiates ovulation, granulosa cells undergo major modification of distal regulatory elements which coincides with cistrome reprogramming of the indispensable orphan nuclear receptor, liver receptor homolog-1 (LRH-1). This cistromic reorganization correlates with the extensive changes in gene expression in ovarian granulosa cells, leading to ovulation. Together, our study yields a transcriptional map of unprecedented detail, delineating ovarian cell differentiation during the initiation of ovulation. It further demonstrates the power of complementary global approaches to accurately characterize molecular events that direct the multiple and rapid changes that characterize reproductive processes. Overall design: Genomic profile of regulatory elements by FAIRE-seq and genomic binding of LRH-1 in mouse granulosa cells before (-OvS) and following the ovulatory signal (+OvS). Transcriptional program of LRH-1 cKO vs control (CTL) granulosa cells before and following the ovulatory signal.