Molecular mechanism of epigenetic regulation of mammalian sex differentiation

• Project/Area Number: 26250037
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokushima
• Principal Investigator: TACHIBANA Makoto 徳島大学, 先端酵素学研究所(次世代), 教授 (80303915)
• Co-Investigator(Renkei-kenkyūsha): TAKEMOTO Keiko 京都大学, ウイルス研究所, 助教 (90243104) ; MIYACHI Hitoshi 京都大学, ウイルス研究所, 技術専門職員 (90599200)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000); Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2015: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2014: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
• Keywords: ヒストン / メチル化 / 性決定 / ヒストン修飾 / エピジェネティクス / 性分化 / エピゲノム

Outline of Final Research Achievements

Epigenetic regulation by covalent modification of histone tails play crucial roles on a wide range of biological processes in mammal. Previously we found that histone demethylation is required for mammalian sex differentiation. Based on this finding, we further studied the roles of epigenetic regulation for sex differentiation. We found that the expression level of mammalian sex-determining gene is finely tuned by the antagonistic activities between histone demethylation and methylation.

Research Products

• [Int'l Joint Research] University of Kansas Medical Center(米国)
• [Int'l Joint Research] University Hospital Freiburg(Germany)
• [Int'l Joint Research] University of Tennessee(米国)
• [Journal Article] A HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia (2016)
  • Author(s): Chakraborty D, Cui W, Rosario GX, Scott RL, Dhakal P, Renaud SJ, Tachibana M, Rumi MAK, Mason CW, Krieg A, *Soares MJ
  • Journal Title: PNAS Volume: 113 Issue: 46
  • DOI: 10.1073/pnas.1612626113
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] PRDM14 drives OCT-3/4 recruitment via active demethylation in the transition from primed to naive pluripotency (2016)
  • Author(s): Okashita N, Suwa Y, Nishimura O, Sakashita N, Kadota, Nagamatsu G, Kawaguchi M, Kashida H, Nakajima A, Tachibana M, *Seki Y
  • Journal Title: Stem Cell Rep Volume: 7 Issue: 6 Pages: 1072-1086
  • DOI: 10.1016/j.stemcr.2016.10.007
  • NAID: 120007037462
  • Peer Reviewed / Open Access
• [Journal Article] Pericentric H3K9me3 formation by HP1 interaction-defective histone methyltransferase Suv39h1 (2016)
  • Author(s): Muramatsu D, Kimura H, Kuboshita K, Tachibana M, *Shinkai Y
  • Journal Title: Cell Struct. Funct. Volume: 41 Pages: 145-152
  • NAID: 130005179827
  • Peer Reviewed
• [Journal Article] Epigenetics of Sex Determination in Mammals Tachibana M. (2016)
  • Author(s): Tachibana M.
  • Journal Title: Reproductive Medicine and Biology Volume: 15 Issue: 2 Pages: 59-67
  • DOI: 10.1007/s12522-015-0223-7
  • Peer Reviewed
• [Journal Article] Development of a general-purpose method for cell purification using Cre/loxP-mediated recombination. (2015)
  • Author(s): Kuroki S, Akiyoshi M, Ideguchi K, Kitano S, Miyachi H, Hirose M, Mise N, Abe K, Ogura A, Tachibana M.
  • Journal Title: Genesis. Volume: 53(6) Issue: 6 Pages: 387-93
  • DOI: 10.1002/dvg.22863
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] H3K9MTase G9a is essential for the differentiation and growth of tenocytes in vitro (2015)
  • Author(s): Wada S, Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, Kimura H, Shinkai Y, Tachibana M, Nifuji A.
  • Journal Title: Histochem Cell Biol. Volume: in press Issue: 1 Pages: 13-20
  • DOI: 10.1007/s00418-015-1318-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic regulation of mammalian sex determination (2015)
  • Author(s): Tachibana M.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 1.2 Pages: 19-23
  • DOI: 10.2152/jmi.62.19
  • NAID: 130005129692
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed
• [Journal Article] The Hypoxia-Inducible Epigenetic Regulators Jmjd1a and G9a Provide a Mechanistic Link between Angiogenesis and Tumor Growth. (2014)
  • Author(s): Ueda J, Ho JC2, Lee KL, Kitajima S, Yang H, Sun W, Fukuhara N, Zaiden N, Chan SL, Tachibana M, Shinkai Y, Kato H ,Poellinger L.
  • Journal Title: Mol. Cell. Biol. Volume: 34 Issue: 19 Pages: 3702-3720
  • DOI: 10.1128/mcb.00099-14
  • Peer Reviewed
• [Journal Article] Transgenic Expression of Map3k4 Rescues T-associated Sex Reversal (Tas) in Mice (2014)
  • Author(s): Warr N, Siggers P, Carréa GA, Bogani D, Brixey R, Akiyoshi M, Tachibana M, Lydia Teboul L, Wells S, Sanderson J and *Greenfield A
  • Journal Title: Hum. Mol. Genetics Volume: 23 Issue: 11 Pages: 3035-3044
  • DOI: 10.1093/hmg/ddu020
  • Peer Reviewed / Open Access
• [Presentation] Role of H3K9 methylation and demethylation enzymes in mouse development (2017)
  • Author(s): Shunsuke Kuroki and Makoto Tachibana
  • Organizer: 11th International Symposium of The Institute Network, Frontiers in Biomedical Sciences
  • Place of Presentation: 徳島大学藤井節郎記念研究センター（徳島県・徳島市）
  • Int'l Joint Research
• [Presentation] ヒストンのメチル化と脱メチル化による生命機能制御 (2016)
  • Author(s): 立花誠
  • Organizer: X染色体研究会
  • Place of Presentation: 鳥取大学医学部臨床講義棟（鳥取県米子市）
  • Year and Date: 2016-03-25
• [Presentation] ヒストンのメチル化修飾による高次生命現象の制御 (2016)
  • Author(s): 立花誠
  • Organizer: 共同利用・共同研究｢酵素学研究拠点｣シンポジウム
  • Place of Presentation: 北里大学薬学部コンベンションホール（東京都港区）
  • Year and Date: 2016-03-07
  • Invited
• [Presentation] H3K9メチル化の動的変動によるほ乳類の発生・分化制御 (2016)
  • Author(s): 立花誠
  • Organizer: 第39回日本分子生物学会年会シンポジウム「発生・老化・疾患をつかさどるクロマチンイベント」
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Invited
• [Presentation] マウス性決定のエピジェネティックな制御機構 (2016)
  • Author(s): 立花誠
  • Organizer: 日本遺伝学会第88回大会シンポジウム「エピジェネティクスの広がり」
  • Place of Presentation: 日本大学国際関係学部（静岡県・三島市）
  • Invited
• [Presentation] Regulation of germ cell development by histone demethylation (2016)
  • Author(s): Shunsuke Kuroki and Makoto Tachibana
  • Organizer: 第1回次世代生命科学の研究会
  • Place of Presentation: 徳島大学藤井節郎記念研究センター（徳島県・徳島市）
• [Presentation] H3K9脱メチル化酵素Jmjd1aとJmjd1bによる雄性生殖細胞の発生制御 (2016)
  • Author(s): 黒木 俊介, 立花 誠
  • Organizer: 第10回日本エピジェネティクス研究会年会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府・豊中市）
• [Presentation] マウス性決定のエピジェネティックな制御機構 (2015)
  • Author(s): 立花誠
  • Organizer: 湯島性分化勉強会
  • Place of Presentation: 東京ガーデンパレス（東京都文京区）
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] マウス性決定のエピジェネティックな制御機構 (2015)
  • Author(s): 立花誠
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 東京一ツ橋学術総合センター（東京都千代田区）
  • Year and Date: 2015-05-25
  • Invited
• [Presentation] エピゲノム調節によるほ乳類の性決定機構 (2014)
  • Author(s): 立花誠
  • Organizer: 第59回日本生殖医学会学術講演会・総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-12-04
  • Invited
• [Presentation] マウス性決定のエピジェネティックな制御機構 (2014)
  • Author(s): 立花誠
  • Organizer: 第32回日本受精着床学会総会・学術講演会
  • Place of Presentation: ハイアット リージェンシー東京（東京都新宿区）
  • Year and Date: 2014-07-31
  • Invited
• [Remarks] 徳島大学先端酵素学研究所 エピゲノム動態学分野 ホームページ
  • URL: https://ouyoukouso01.ait231.tokushima-u.ac.jp/
• [Remarks] 徳島大学疾患酵素学研究センター 立花研究室
  • URL: https://ouyoukouso01.ait231.tokushima-u.ac.jp/