Integrated Analysis of Transcriptome and Histone Modifications in Granulosa Cells During Ovulation in Female Mice
| Autor: | Ryo Maekawa, Hiroshi Tamura, Shun Sato, Yasuyuki Ohkawa, Masahiro Shinagawa, Yumiko Doi-Tanaka, Yuichiro Shirafuta, Isao Tamura, Yumiko Mihara, Haruka Takagi, Toshiaki Taketani, Norihiro Sugino |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ovulation
0301 basic medicine endocrine system medicine.medical_specialty media_common.quotation_subject Biology Chorionic Gonadotropin Human chorionic gonadotropin Histones Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Gene expression medicine Animals Equine chorionic gonadotropin media_common Granulosa Cells Gene Expression Profiling Luteinizing Hormone Chromatin Cell biology Histone Code Mice Inbred C57BL Systems Integration Luteinization 030104 developmental biology Histone 030220 oncology & carcinogenesis biology.protein Female sense organs Luteinizing hormone Protein Processing Post-Translational |
| Zdroj: | Endocrinology. 162 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endocr/bqab128 |
| Popis: | The ovulatory luteinizing hormone (LH) surge induces rapid changes of gene expression and cellular functions in granulosa cells (GCs) undergoing luteinization. However, it remains unclear how the changes in genome-wide gene expression are regulated. H3K4me3 histone modifications are involved in the rapid alteration of gene expression. In this study, we investigated genome-wide changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization. GCs were obtained from mice treated with equine chorionic gonadotropin (hCG) before, 4 hours, and 12 hours after human chorionic gonadotropin injection. RNA-sequencing identified a number of upregulated and downregulated genes, which could be classified into 8 patterns according to the time-course changes of gene expression. Many genes were transiently upregulated or downregulated at 4 hours after hCG stimulation. Gene Ontology terms associated with these genes included steroidogenesis, ovulation, cumulus-oocyte complex (COC) expansion, angiogenesis, immune system, reactive oxygen species (ROS) metabolism, inflammatory response, metabolism, and autophagy. The cellular functions of DNA repair and cell growth were newly identified as being activated during ovulation. Chromatin immunoprecipitation–sequencing revealed a genome-wide and rapid change in H3K4me3 during ovulation. Integration of transcriptome and H3K4me3 data identified many H3K4me3-associated genes that are involved in steroidogenesis, ovulation, COC expansion, angiogenesis, inflammatory response, immune system, ROS metabolism, lipid and glucose metabolism, autophagy, and regulation of cell size. The present results suggest that genome-wide changes in H3K4me3 after the LH surge are associated with rapid changes in gene expression in GCs, which enables GCs to acquire a lot of cellular functions within a short time that are required for ovulation and luteinization. |
| Databáze: | OpenAIRE |
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