GSE167939
Integrated analysis of transcriptome and histone modifications in granulosa cells during ovulation in female mice [RNA-seq]
The ovulatory LH surge induces rapid changes of transcriptome and cellular functions in granulosa cells (GCs) undergoing luteinization.  However, it remains unclear how the changes in genome-wide gene expression are regulated.  The changes of trimethylation of lysine 4 on histone H3 (H3K4me3) is associated with the rapid alteration of gene expression.  In this study, we genome-widely investigated the changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization during ovulation.  GCs were obtained from mice treated with equine chorionic gonadotropin (eCG) before, 4 h and 12 h after human (h)CG injection.  RNA-sequence identified a number of up- or down-regulated genes, which can be classified into six patterns according to the time-course changes of gene expression.  A number of genes showed a transient up- or down-regulation at 4 h after hCG stimulation.  Gene ontology analysis revealed that they were involved in the regulation of steroidogenesis, ovulation, COC expansion, angiogenesis, immune system, ROS metabolism, inflammatory response, and metabolisms.  The newly identified cellular functions, DNA repair, autophagy and cell growth were found to be activated during ovulation.  ChIP-sequence revealed a genome-wide and rapid change of H3K4me3 during ovulation.  Integration of transcriptome and H3K4me3 data identified a number of H3K4me3-regulated genes, which were involved in the regulation of a lot of cellular functions for ovulation and luteinization.  The present study demonstrated that genome-wide changes of H3K4me3 might contribute to the rapid change of genome-wide gene expression, which enables GCs acquire a lot of cellular functions within a short time for ovulation and luteinization. Overall design: mRNA profiles of mouse granulosa cells undergoing luteinization during ovulation