Changes in histone modifications and DNA methylation of the Cyp11a1(P450scc) promoter region in rat granulosa cells undergoing

• Project/Area Number: 15K20146
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: OKADA Maki 山口大学, 医学部附属病院, 助教 (90736159)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: エピジェネティクス / プロゲステロン合成 / Cyp11a1 / エピジェネティクス制御 / シグナル伝達 / 発現制御 / ゲノム

Outline of Final Research Achievements

The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes in granulosa cells. Cyp11a1 is rapidly induced after the LH surge. The rapid shift of estrogen synthesis is to progesterone synthesis after the LH surge is crucial for ovulation and the following luteinization.
We revealed that histone modifications and chromatin remodeling of the Cyp11a1 promoter region are altered in GCs undergoing luteinization during ovulation. These epigenetic changes are involved in the rapid increase of Cyp11a1 expression after the ovulatory LH surge. Our results also show that the C/EBPβ binding site in the proximal promoter region is a novel regulatory region of Cyp11a1 gene in rats.

Research Products

• [Journal Article] Epigenetic changes of the Cyp11a1 promoter region in granulosa cells undergoing lutanization during ovulation in rats (2016)
  • Author(s): Maki Okada, Lifa Lee, Ryo Maekawa, Shun Sato, Takuya Kajimura, Masahiro Shinagawa, Isao Tamura, Toshiaki Taketani, Hiromi Asada, Hiroshi Tamura and Norihiro Sugino
  • Journal Title: Endocrinology Volume: 157 Issue: 9 Pages: 3344-3354
  • DOI: 10.1210/en.2016-1264
  • NAID: 130007024722
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation. (2016)
  • Author(s): Maekawa R, Lee L, Okada M, Asada H, Shinagawa M, Tamura I, Sato S, Tamura H, Sugino N
  • Journal Title: J Ovarian Res Volume: 15 Issue: 1 Pages: 1-9
  • DOI: 10.1186/s13048-016-0225-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tissue-Specific Expression of Estrogen Receptor 1 Is Regulated by DNA Methylation in a T-DMR (2016)
  • Author(s): Maekawa R, Sato S, Okada M, Lee L, Tamura I, Jozaki K, Kajimura T, Asada H, Yamagata Y, Tamura H, Yamamoto S, Sugino N
  • Journal Title: Mol Endocrinol Volume: 30 Issue: 3 Pages: 335-47
  • DOI: 10.1210/me.2015-1058
  • NAID: 130007024986
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Changes in histone modification, DNA methylation and C/EBPb binding of the Cyp11a1 promoter region in rat granulosa cells undergoing luteinization during ovulation. (2015)
  • Author(s): Maki Okada, Ryo Maekawa, Hiroshi Tamura, Norihiro Sugino
  • Organizer: SSR (米国生殖学会議)
  • Place of Presentation: プエルトリコ・Puerto Rico Convention Center
  • Year and Date: 2015-06-18
  • Int'l Joint Research
• [Presentation] ラット顆粒膜細胞の黄体化に伴うCyp11a1(P450scc)遺伝子発現のepigenetics制御 (2015)
  • Author(s): 岡田真紀，李理華，前川亮，佐藤俊，品川征大，城﨑 幸介, 浅田裕美，山縣芳明，田村博史，杉野法広
  • Organizer: 第9回エピジェネティクス研究会
  • Place of Presentation: 東京・学術総合センター一橋講堂
  • Year and Date: 2015-05-25
• [Presentation] Changes in histone modifications and DNA methylation of the Cyp11a1(P450scc) promoter region in rat granulosa cells undergoing luteinization during ovulation (2015)
  • Author(s): Maki Okada, Kosuke Josaki, Ryo Maekawa, Hiroshi Tamura, and Norihiro Sugino
  • Organizer: IFFS(国際生殖医学会)
  • Place of Presentation: 神奈川・パシフィコ横浜
  • Year and Date: 2015-04-26
  • Int'l Joint Research
• [Presentation] ラット顆粒膜細胞の黄体化に伴うCyp11a1(P450scc)遺伝子発現のepigenetics制御 (2015)
  • Author(s): 岡田真紀，李理華，品川征大，前川亮，浅田裕美，佐藤俊，山縣芳明，田村博史，杉野法広
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: 東京・ホテルニューオータニ東京
  • Year and Date: 2015-04-23