RRC ID 44179
著者 Lee L, Asada H, Kizuka F, Tamura I, Maekawa R, Taketani T, Sato S, Yamagata Y, Tamura H, Sugino N.
タイトル Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in rats.
ジャーナル Endocrinology
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.
巻・号 154(1)
ページ 458-70
公開日 2013-1-1
DOI 10.1210/en.2012-1610
PII en.2012-1610
PMID 23183184
MeSH Animals Aromatase / genetics* Chorionic Gonadotropin / pharmacology DNA Methylation / drug effects DNA Methylation / genetics* Female Granulosa Cells / drug effects Granulosa Cells / metabolism* Histones / drug effects Histones / metabolism* Horses Luteinization / drug effects Luteinization / genetics Ovulation / drug effects Ovulation / genetics Phosphoproteins / genetics* Promoter Regions, Genetic / drug effects Promoter Regions, Genetic / genetics* Rats
IF 3.934
引用数 38
WOS 分野 ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 RLC-16