title: Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in rats.
abstract: The ovulatory LH surge induces rapid up-regulation of steroidogenic acute regulatory (StAR) protein and rapid down-regulation of aromatase (Cyp19a1) in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic mechanisms including histone modifications are involved in the rapid changes of StAR and Cyp19a1 gene expression. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and after human (h)CG injection. StAR mRNA levels rapidly increased after hCG injection, reached a peak at 4 h, and then remained higher compared with 0 h until 12 h. Cyp19a1 mRNA levels gradually decreased after hCG injection and reached their lowest level at 12 h. A chromatin immunoprecipitation assay revealed that levels of histone-H4 acetylation (Ac-H4) and trimethylation of histone-H3 lysine-4 (H3K4me3) increased whereas H3K9me3 and H3K27me3 decreased in the StAR promoter after hCG injection. On the other hand, the levels of Ac-H3 and -H4 and H3K4me3 decreased, and H3K27me3 increased in the Cyp19a1 promoter after hCG injection. Chromatin condensation, which was analyzed using deoxyribonuclease I, decreased in the StAR promoter and increased in the Cyp19a1 promoter after hCG injection. A chromatin immunoprecipitation assay also showed that binding activities of CAATT/enhancer-binding protein β to the StAR promoter increased and binding activities of phosphorylated-cAMP response element binding protein to the Cyp19a1 promoter decreased after hCG injection. These results provide in vivo evidence that histone modifications are involved in the rapid changes of StAR and Cyp19a1 gene expression by altering chromatin structure of the promoters in GCs undergoing luteinization during ovulation.
authors.affiliation: Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
authors.forename: Lifa
authors.initials: L
authors.lastname: Lee
authors.forename: Hiromi
authors.initials: H
authors.lastname: Asada
authors.forename: Fumie
authors.initials: F
authors.lastname: Kizuka
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.forename: Ryo
authors.initials: R
authors.lastname: Maekawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Taketani
authors.forename: Shun
authors.initials: S
authors.lastname: Sato
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sugino
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D006736:Horses; D034461:Luteinization / Q000187:drug effects / Q000235:genetics; D010060:Ovulation / Q000187:drug effects / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006063:Chorionic Gonadotropin; D006657:Histones; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D001141:Aromatase