Mechanism of adrenocortical differentiation by exchange and conversion of enhancers

• Project/Area Number: 21249018
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: MOROHASHI Ken-ichirou 九州大学, 大学院・医学研究院, 主幹教授 (30183114)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥34,060,000 (Direct Cost: ¥26,200,000、Indirect Cost: ¥7,860,000); Fiscal Year 2011: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2010: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
• Keywords: 副腎皮質 / エンハンサー / クロマチン構造 / ヒストン / 組織特異的エンハンサー / エピジェネティクス / ChIP-sequence / ケロマチン構造

Research Abstract

Ad4BP/SF-1, a member of nuclear receptor superfamily, plays pivotal role in differentiation and function of the adrenal cortex through regulating various target genes. It has been hypothesized that active enhancers should be exchanged or selected through conversion of chromatin structure when Ad4BP/SF-1 functions during the tissue development. In the present study, we performed ChIP-sequence analyses of theDNA recovered with antibodies for Ad4BP/SF-1 and modified histones. As the consequence, it was found that Ad4BP/SF-1 regulates glycolytic gene expression through binding to enhancers localized in and around the genes.

Research Products

• [Journal Article] WNT family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbesterol exposure in mice (2012)
  • Author(s): T. Nakamura, S. Miyagawa, Y. Katsu, H. Watanabe, T. Mizutani, T. Sato, K. Morohashi, T. Takeuchi, T. Iguchi.
  • Journal Title: Toxicology Volume: 296 Pages: 13-19
  • Peer Reviewed
• [Journal Article] Cbx2, a polycomb group gene, is required for Sry gene expression in mice (2012)
  • Author(s): Y. Katoh-Fukui, K. Miyabayashi, T. Komatsu, A. Owaki, T. Baba, Y. Shima, T. Kidokoro, Y. Kanai, A. Schedl, D. Wilhelm, P. Koopman, Y. Okuno, K. Morohashi.
  • Journal Title: Endocrinology Volume: 153 Pages: 913-924
  • Peer Reviewed
• [Journal Article] Identification of enhancer specific for fetal Leydig cells in Ad4BP/SF-1 gene (2012)
  • Author(s): Y. Shima, K. Miyabayashi, T. Baba, H. Otake, S. Oka, M. Zubair, K. Morohashi.
  • Journal Title: Endocrinology Volume: 153 Pages: 417-425
  • Peer Reviewed
• [Journal Article] SF-1 expression during adrenal development and tumorigenesis. Gardiner JR (2012)
  • Author(s): Y Shima, K. Morohashi, A. Swain
  • Journal Title: Mol. Cell. Endocrinol Volume: 351 Pages: 12-18
  • Peer Reviewed
• [Journal Article] DNA methylation of intronic enhancers directs tissue-specific expression of Steroidogenic Factor 1/Adrenal 4 Binding Protein (2011)
  • Author(s): E. A. Hoivik, T. E. Bjanesoy, O. Mai, S. Okamoto, Y. Minokoshi, Y. Shima, K. Morohashi, U. Boehm, and M. Bakke
  • Journal Title: Endocrinology Volume: 152 Pages: 2100-2112
  • Peer Reviewed
• [Journal Article] The fetal and adult adrenal cortex (2011)
  • Author(s): K. Morohashi and M. Zubair.
  • Journal Title: Mol. Cell. Endocrinol. Volume: 336 1 Pages: 193-197
  • Peer Reviewed
• [Journal Article] Identification of enhancer specific for fetal Leydig cells in Ad4BP/SF-1 gene (2011)
  • Author(s): Yuichi Shima, et al
  • Journal Title: Endocrinology Volume: 153 Issue: 1 Pages: 417-425
  • DOI: 10.1210/en.2011-1407
  • Peer Reviewed
• [Journal Article] DNA methylation of intronic enhancers directs tissue-specific expression of Steroidogenic Factor 1/Adrenal 4 Binding Protein (SF-1/Ad4BP) (2011)
  • Author(s): Erling A.Hoivik, et al
  • Journal Title: Endocrinology Volume: 152 Issue: 5 Pages: 2100-2112
  • DOI: 10.1210/en.2010-1305
  • Peer Reviewed
• [Journal Article] DNA Methylation of Intronic Enhancers Directs Tissue-Specific Expression of Steroidogenic Factor 1/Adrenal 4 Binding Protein(SF-1/Ad4BP). (2011)
  • Author(s): Erling A, et al.
  • Journal Title: Endocrinology Volume: 151(In press)
  • Peer Reviewed
• [Journal Article] The fetal and adult adrenal cortex (2011)
  • Author(s): Morohashi K, Zubair M
  • Journal Title: Mol.Cell.Endocrinol. Volume: 336 Pages: 193-197
  • Peer Reviewed
• [Journal Article] Abnormal epithelial cell polarity and migration of Emx2 KO embryonic gonads induced by ectopic EGFR expression (2010)
  • Author(s): M. Kusaka, Y. Katoh-Fukui, H. Ogawa, K. Miyabayashi, T. Baba, N. Sugiyama, Y. Sugimoto, Y. Okuno, R. Kodama, A. Iizuka-Kogo, T. Senda, S. Aizawa, K. Morohashi.
  • Journal Title: Endocrinol Volume: 151 Pages: 5893-5904
  • Peer Reviewed
• [Journal Article] Production and characterization of monoclonal antibodies to germ cells (2010)
  • Author(s): C. Yokoyama, Y. Katoh-Fukui, K. Morohashi, D. Konno, M. Azauma, and T. Tachibana.
  • Journal Title: Hybridoma Volume: 29 Pages: 53-57
  • Peer Reviewed
• [Journal Article] Abnormal epithelial cell polarity and migration of Emx2 KO embryonic gonads induced by ectopic EGFR expression (2010)
  • Author(s): Kusaka M, et al.
  • Journal Title: Endocrinology Volume: 151 Pages: 5893-5904
  • Peer Reviewed
• [Journal Article] Production and characterization of monoclonal antibodies to germ cells. (2010)
  • Author(s): Chikako Yokoyama, et al.
  • Journal Title: Hybridoma 29 Pages: 53-57
  • Peer Reviewed
• [Journal Article] Transcriptional suppression by transient recruitment of ARIP4 to sumoylated nuclear receptor Ad4BP/SF-1 (2009)
  • Author(s): H. Ogawa, T. Komatsu, Y. Hiraoka, and K. Morohashi.
  • Journal Title: Mol. Biol. Cell Volume: 20 Pages: 4235-4245
  • Peer Reviewed
• [Journal Article] Transgenic expression of Ad4BP/SF-1 in fetal adrenal progenitor cells leads to ectopic adrenal formation (2009)
  • Author(s): M. Zubair, S. Oka, K. L. Parker, and K. Morohashi
  • Journal Title: Mol Endocrinol Volume: 23 Pages: 1657-1667
  • Peer Reviewed
• [Journal Article] Generation of rat monoclonal antibodies specific for Ad4BP/SF-1 (2009)
  • Author(s): C. Yokoyama, T. Komatsu, H. Ogawa, K. Morohashi, M. Azuma, and T. Tachibana
  • Journal Title: Hybridoma Volume: 28 Pages: 113-119
• [Journal Article] A critical time window of Sry action in gonadal sex determination (2009)
  • Author(s): R. Hiramatsu, S. Matoba, M. Fujisawa, M. Kanai-Azuma, N. Tsunekawa, M. Kurohmaru, K. Morohashi, D. Wilhelm, P. Koopman, Y. Kanai.
  • Journal Title: Development Volume: 136 Pages: 129-138
  • Peer Reviewed
• [Journal Article] A critical time window of Sry action in gonadal sex determination. (2009)
  • Author(s): Ryuji Hiramatsu, et al.
  • Journal Title: Development 136 Pages: 129-138
  • Peer Reviewed
• [Journal Article] Generation of rat monoclonal antibodies specific for Ad4BP/SF-1. (2009)
  • Author(s): Chikako Yokoyama, et al.
  • Journal Title: Hybridoma 28 Pages: 113-119
  • Peer Reviewed
• [Journal Article] Transgenic expression of Ad4BP/SF-1 in fetal adrenal progenitor cells leads to ectopic adrenal formation. (2009)
  • Author(s): Mohamad Zubair, et al.
  • Journal Title: Mol Endocrinol 23 Pages: 1657-1667
  • Peer Reviewed
• [Journal Article] Transcriptional suppression by transient recruitment of ARIP4 to sumoylated nuclear receptor Ad4BP/SF-1. (2009)
  • Author(s): Hidesato Ogawa, et al.
  • Journal Title: Mol Biol Cell 20 Pages: 4235-4245
  • Peer Reviewed
• [Journal Article] Steroid hormones and the development of reproductive organs
  • Author(s): K. Morohashi, M. Tanaka
  • Journal Title: Sexual Development. in press. Review
  • Peer Reviewed
• [Presentation] 胎仔型ライディッヒ細胞特異的Ad4BP/SF-1遺伝子ノックアウトマウスの解析 (2011)
  • Author(s): 嶋雄一, その他
  • Organizer: 第19回日本ステロイドホルモン学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-11-26
• [Presentation] RNA-SeqおよびChIP-Seq法によるAd4BP/SF-1標的遺伝子の同定 (2011)
  • Author(s): 馬場崇, その他
  • Organizer: 第4回性差生物医学研究会
  • Place of Presentation: 山口大学
  • Year and Date: 2011-11-21
• [Presentation] 生殖腺におけるステロイドホルモン産生 (2011)
  • Author(s): 諸橋憲一郎
  • Organizer: 第6回日本生殖内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-19
• [Presentation] 生殖腺におけるステロイドホルモン産生 (2011)
  • Author(s): 諸橋憲一郎
  • Organizer: 第6回日本生殖内分泌学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-11-19
• [Presentation] 胎仔型ライディッヒ細胞の生理学的機能の解明 (2011)
  • Author(s): 嶋雄一、諸橋憲一郎
  • Organizer: 第84回日本内分泌学会
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 2011-04-21
• [Presentation] 胎仔型ライディッヒ細胞の生理学的機能の解明 (2011)
  • Author(s): 嶋雄一、諸橋憲一郎
  • Organizer: 第84回日本内分泌学会
  • Place of Presentation: 神戸
• [Presentation] Functional characterization of fetal Leydig cells by cell-specific disruption of Ad4BP/SF-1 gene (2011)
  • Author(s): 嶋雄一, その他
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Identification of Ad4BP/SF-1 target genes by ChIP-Seq in Y-1 adrenocortical cells (2011)
  • Author(s): 馬場崇, その他
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] RNA-Seq解析による胎仔型および成獣型ライディッヒ細胞特異的発現マーカー遺伝子の探索 (2011)
  • Author(s): 宮林香奈子, その他
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 生殖腺の性差構築 (2011)
  • Author(s): 諸橋憲一郎
  • Organizer: 第4回 日本性差医学・医療学会
  • Place of Presentation: 下関
• [Presentation] Tissue-specific Enhancers of Ad4BP/SF-1 (2010)
  • Author(s): K. Morohashi
  • Organizer: Gene Official Satellite Symposia of ICE2010
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-30
• [Presentation] 生殖腺の発生と性分化メカニズム (2010)
  • Author(s): 諸橋憲一郎
  • Organizer: 第10回日本内分泌学会中国支部学術集会
  • Place of Presentation: 宇部
  • Year and Date: 2010-03-06
• [Presentation] ステロイドホルモン産生組織(副腎皮質)の分化メカニズム (2010)
  • Author(s): 諸橋憲一郎, 他
  • Organizer: 第21回日本臨床化学会九州支部総会第55回日本臨床検査医学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2010-02-13
• [Presentation] 性差を構成する遺伝子発現 (2010)
  • Author(s): 諸橋憲一郎
  • Organizer: 第10回 旭川ウインターシンポジウム
  • Place of Presentation: 旭川
  • Year and Date: 2010-01-30
• [Presentation] Cell lineage of fetal Leydig cell and adult Leydig cell (2010)
  • Author(s): 嶋雄一、馬場崇、宮林香奈子、栗原淑子、諸橋憲一郎
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-01-30
• [Presentation] The Keith Parker Memorial Lecture. Ad4BP/SF-1 as the key factor for steroidogenic cell development (2010)
  • Author(s): K. Morohashi
  • Organizer: 14th Adrenal Cortex Conference
  • Place of Presentation: San Diego, USA
• [Presentation] Implication of Ad4BP/SF-1 into Adrenal Development (2010)
  • Author(s): K. Morohashi, Y. Shima, K. Miyabayashi, H. Otake, T. Baba, M. Zubair
  • Organizer: 14th International Congress of Endocrinology, ICE2010
  • Place of Presentation: Kyoto, Japan
• [Presentation] 生殖腺の性差構築 (2010)
  • Author(s): 諸橋憲一郎
  • Organizer: 第4回日本性差医学・医療学会
  • Place of Presentation: 下関
• [Presentation] Transcriptomic analysis of fetal Leydig cells (2010)
  • Author(s): Y. Shima, T. Baba, K. Miyabayashi, H. Otake, Y. Kurihara, K. Morohashi
  • Organizer: 第33回日本分子生物学会、第83回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] ステロイド産生細胞の発生 (2010)
  • Author(s): 諸橋憲一郎
  • Organizer: 第28回内分泌代謝サマーセミナー
  • Place of Presentation: 長崎
• [Presentation] Molecular and Cellular Mechanisms of Testis Differentiation (2010)
  • Author(s): Morohashi K
  • Organizer: Gordon Research Conference, 2010 Reproductive Tract Biology
  • Place of Presentation: New Hampshire, USA
• [Presentation] Common Steroidogenic Primordia in Gonadal and Adrenal Morphogenesis Lineage of Testicular Leydig cells and Adrenal Cortex (2010)
  • Author(s): Morohashi K, et al.
  • Organizer: 43 rd Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: Milwaukee, USA
• [Presentation] Ad4BP/SF-1 as the key factor for steroidogenic cell development (2010)
  • Author(s): Morohashi K
  • Organizer: 14th Adrenal Cortex Conference
  • Place of Presentation: San Diego, USA
• [Presentation] Transcriptomic analysis of fetal Leydig cells (2010)
  • Author(s): 嶋雄一、諸橋憲一郎, 他
  • Organizer: 第33回 日本分子生物学会、第83回 日本生化学会
  • Place of Presentation: 神戸
• [Presentation] Expression profile of steroidogenic genes in the fetal LEydig cells (2010)
  • Author(s): 宮林香奈子、諸橋憲一郎, 他
  • Organizer: 第33回 日本分子生物学会、第83回 日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 胎仔ライディッヒ細胞と成獣ライディッヒ細胞の細胞系譜の解明 (2009)
  • Author(s): 嶋雄一、諸橋憲一郎
  • Organizer: 第17回日本ステロイドホルモン学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] マウス胎仔ライディッヒ細胞分化過程におけるArx遺伝子の機能 (2009)
  • Author(s): 宮林香奈子、杉山紀之、馬場崇、嶋雄一、福井由宇子、小川英知、杉本幸彦、諸橋憲一郎
  • Organizer: 第17回日本ステロイドホルモン学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] Ad4BP/SF-1の胎仔ライディッヒ細胞特定期エンハンサー結合因子の同定 (2009)
  • Author(s): 関原早苗、嶋雄一、馬場崇、宮林香奈子、諸橋憲一郎
  • Organizer: 第17回日本ステロイドホルモン学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] ダイオキシン受容体(AhR)の生殖腺における機能 : 性ステロイドホルモンの合成 (2009)
  • Author(s): 馬場崇、三村純正、嶋雄一、中村直人、大脇亜希子、大島基彦、原田信広、山本雅之、藤井義明、諸橋憲一郎
  • Organizer: 第17回日本ステロイドホルモン学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] Molecular mechanisms for the functions and structures of tissue specific enhancers (2009)
  • Author(s): Y. Shima, T. Baba, K. Miyabayashi, M. Zubair, K. Morohashi
  • Organizer: Fifth international Symposium on the biology of vertebrate sex determination
  • Place of Presentation: Kona, Hawaii, USA
• [Presentation] 生殖腺の発生と性分化のメカニズム (2009)
  • Author(s): 諸橋憲一郎、馬場崇、宮林香奈子、大竹博之、嶋雄一
  • Organizer: 第54回日本生殖医学会
  • Place of Presentation: 金沢
• [Presentation] Genetic Program of Gonad Differenti (2009)
  • Author(s): 諸橋憲一郎
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
• [Presentation] ステロイドホルモン産生組織の分化とAd4BP/SF-1遺伝子の組織特異的エンハンサー選択 (2009)
  • Author(s): 諸橋憲一郎
  • Organizer: 第13回 小児内分泌研究会
  • Place of Presentation: 函館
• [Presentation] 生殖腺の発生と性分化のメカニズム (2009)
  • Author(s): 諸橋憲一郎, 他
  • Organizer: 第54回 日本生殖医学会
  • Place of Presentation: 金沢
• [Presentation] Aug 15-19, Andover, Andover, New Hampshire
  • Author(s): Keynote Lecture, Molecular and Cellular Mechanisms of Testis Differentiation. K. Morohashi
  • Organizer: Gordon Research Conference, 2010 Reproductive Tract Biology
  • Place of Presentation: USA
• [Presentation] Milwaukee
  • Author(s): Lineage of Testicular Leydig cells and Adrenal Cortex. K. Morohashi, Z. Mohamad, T. Baba, K. Miyabayashi, H. Otake, Y. Shima
  • Organizer: 43 rd Annual Meeting of the Society for the Study of Reproduction July 28-Aug
  • Place of Presentation: USA, Invited Speaker
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