Epigenetic regulation of mammalian spermatogenesis

2012 Fiscal Year Final Research Report

• Project Area: The germline: its developmental cycle and epigenome network
• Project/Area Number: 20062014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KOSEKI Haruhiko 独立行政法人理化学研究所, 免疫器官形成研究グループ, グループディレクター (40225446)
• Co-Investigator(Kenkyū-buntansha): SHIBAHARA Kei-ichi 国立遺伝学研究所, 総合遺伝研究系, 准教授 (20263098)
• Co-Investigator(Renkei-kenkyūsha): TAKADA Yuki 独立行政法人理化学研究所, 免疫器官形成研究グループ, 研究員 (40392013)
• Project Period (FY): 2008 – 2012
• Keywords: マウス / 精子形成 / 減数分裂 / ヘテロクロマチン / セントロメア / ヒストン修飾 / ポリコム群

Research Abstract

Although it is well accepted that spermatogenesis and spermiogenesis are accompanied by sequential changes of chemical modifications of histone tails, their biological impacts and underlying mechanisms are poorly understood until now. In this study, we focus on the role of H3K9 methylation and H2A monoubiquitination mediated by Polycomb complexes during meiotic prophase and histone hyperacetylation in round spermatids. We found H3K9 methylation and its recognition played critical role to regulate centromere dynamics and chromosome pairing. Polycomb turned out to possess distinct labor for chromosome pairing by promoting telomere/nuclear envelope interaction. We finally demonstrated mammalian ortholog of yeast piccolo complexes were essential for global histone hyperacetylation in round spermatids and for histone/TP replacement.

Research Products

• [Journal Article] H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions. (2012)
  • Author(s): Ku M, Jaffe JD, Koche RP, Rheinbay E, Endoh M, Koseki H, Carr SA, Bernstein BE.
  • Journal Title: Genome Biol. Volume: 13 Pages: R85
  • Peer Reviewed
• [Journal Article] Histone H2A Mono-Ubiquitination Is a Crucial Step to Mediate PRC1-Dependent Repression of Developmental Genes to Maintain ES Cell Identity. (2012)
  • Author(s): Endoh M, Endo TA, Endoh T, Isono K, Sharif J, Ohara O, Toyoda T, Ito T, Eskeland R, Bickmore WA, Vidal M, Bernstein BE, Koseki H.
  • Journal Title: PLoS Genet. Volume: 8 Pages: e1002774
  • DOI: doi: 10.1371/journal.pgen.1002774
  • Peer Reviewed
• [Journal Article] RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells. (2012)
  • Author(s): Hisada K, Sanchez C, Endo TA, Endoh M, Roman-Trufero M, Sharif J, Koseki H, Vidal M.
  • Journal Title: Mol Cell Biol. Volume: 32 Pages: 1139-49
  • Peer Reviewed
• [Journal Article] HP1γ links histone methylation marks to meiotic synapsis in mice. (2011)
  • Author(s): Takada Y, Naruse C, Costa Y, Shirakawa T, Tachibana M, Sharif J, Kezuka-Shiotani F, Kakiuchi D, Masumoto H, Shinkai Y, Ohbo K, Peters AH, Turner JM, Asano M, Koseki H.
  • Journal Title: Development Volume: 138 Pages: 4207-17
  • Peer Reviewed
• [Journal Article] Polycomblike 2 facilitates the recruitment of PRC2 Polycomb group complexes to the inactive X chromosome and to target loci in embryonic stem cells. (2011)
  • Author(s): Casanova M, Preissner T, Cerase A, Poot R, Yamada D, Li X, Appanah R, Bezstarosti K, Demmers J, Koseki H, Brockdorff N.
  • Journal Title: Development Volume: 138 Pages: 1471-82
  • Peer Reviewed
• [Journal Article] Mammalian Polycomblike Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate Polycomb activity at both the Hox gene cluster and at Cdkn2a genes. (2011)
  • Author(s): Li X, Isono KI, Yamada D, Endo TA, Endoh M, Shinga J, Mizutani-Koseki Y, Otte AP, Casanova M, Kitamura H, Kamijo T, Sharif J, Ohara O, Toyada T, Bernstein BE, Brockdorff N, Koseki H.
  • Journal Title: Mol Cell Biol. Volume: 31 Pages: 351-364
  • Peer Reviewed
• [Journal Article] Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages. Spermatogenic Disruptions at Three Meiotic Stages in Hybrid Males Between House Mouse Subspecies or Species. (2010)
  • Author(s): Oka A, Mita A, Takada Y, Koseki H, Shiroishi T.
  • Journal Title: Genetics Volume: 186 Pages: 339-351
  • Peer Reviewed
• [Journal Article] ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency. (2010)
  • Author(s): Pereira CF, Piccolo FM, Tsubouchi T, Sauer S, Ryan NK, Bruno L, Landeira D, Santos J, Banito A, Gil J, Koseki H, Merkenschlager M, Fisher AG.
  • Journal Title: Cell Stem Cell. Volume: 6 Pages: 547-556
  • Peer Reviewed
• [Journal Article] Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells. (2010)
  • Author(s): Majewski IJ, Ritchie ME, Phipson B, Corbin J, Pakusch M, Ebert A, Busslinger M, Koseki H, Hu Y, Smyth GK, Alexander WS, Hilton DJ, Blewitt ME.
  • Journal Title: Blood. Volume: 116 Pages: 731-739
  • Peer Reviewed
• [Journal Article] PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. (2008)
  • Author(s): Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K, Brykczynska U, Kolb C, Otte AP, Koseki H, Orkin SH, van Lohuizen M, Peters AH.
  • Journal Title: Nat Genet. Volume: 40 Pages: 411-20
  • Peer Reviewed
• [Presentation] Polycomb potentiates Meis2 activation in midbrain by mediating precursory interaction of promoter with tissue-specific enhance (2013)
  • Author(s): 古関明彦
  • Organizer: RCAI-Michigan Joint Workshop
  • Place of Presentation: 米国、アナーバー
  • Year and Date: 2013-01-16
• [Presentation] Mechanisms underlying Polycomb repression (2012)
  • Author(s): 古関明彦
  • Organizer: 文部科学省新学術領域 細胞運命制御
  • Place of Presentation: 日本、京都
  • Year and Date: 2012-11-06
• [Presentation] ポリコム群の機能発現メカニズム (2012)
  • Author(s): 古関明彦
  • Organizer: 第4回シグナルネットワーク研究会
  • Place of Presentation: 日本、大阪
  • Year and Date: 2012-05-18
• [Presentation] SAM domain-mediated polymerization of mammalian polyhomeotic homologues mediates recruitment of PRC1 to Polycomb target genes and their condensation (2011)
  • Author(s): 古関明彦
  • Organizer: 3rd X-inactivation meeting
  • Place of Presentation: 英国、オックスフォード
  • Year and Date: 2011-07-23
• [Presentation] Polycomb-dependent regulation for differentiation programs of stem cells and progenitors (2011)
  • Author(s): 古関明彦
  • Organizer: アジアエピゲノムワークショップ/ 第五回日本エピジェネティクス研究会
  • Place of Presentation: 日本、熊本市
  • Year and Date: 2011-05-19
• [Presentation] Polycomb-dependent regulation for differentiation programs of stem cells and progenitors (2010)
  • Author(s): 古関明彦
  • Organizer: 第16回国際分化学会国際会議
  • Place of Presentation: 日本、奈良市
  • Year and Date: 2010-11-16
• [Presentation] The role of Polycomb body to mediate Hox repression (2010)
  • Author(s): 古関明彦
  • Organizer: 東京大学分子細胞生物学研究所 核内情報研究分野 シンポジウム
  • Place of Presentation: 日本、東京都
  • Year and Date: 2010-11-02
• [Presentation] 遺伝現象におけるエピジェネティック制御とリプログラミング (2010)
  • Author(s): 古関明彦
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 日本、大阪市
  • Year and Date: 2010-05-19
• [Presentation] HP1g links histone H3K9 methylation to homologus chromosome pairing during melotic prophase (2009)
  • Author(s): 古関明彦
  • Organizer: The Epigenetics 2009 Australian Scientific Conference@Epigenetics and Development
  • Place of Presentation: オーストラリア、ブリスベン
  • Year and Date: 2009-12-02
• [Presentation] ES細胞におけるポリコーム群の動き (2009)
  • Author(s): 古関明彦
  • Organizer: 第42回日本発生生物学会年会
  • Place of Presentation: 日本、京都
  • Year and Date: 2009-05-29
• [Presentation] Histone H2A ubiquitinylation subdivides bivalent genes into PRC1-dependent and -independent domains in ES cells (2008)
  • Author(s): 古関明彦
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会、合同大会
  • Year and Date: 2008-12-09
• [Presentation] Polycom repression mediates pluripotency of ES cells (2008)
  • Author(s): 古関明彦
  • Organizer: Cold Spring Harbor Laboratory
  • Place of Presentation: アメリカ、ニューヨーク
  • Year and Date: 2008-10-31
• [Presentation] Mouse development: embryogenesis (2008)
  • Author(s): 古関明彦
  • Organizer: EMBO Practical Course on Anatomy and Embryology of the Mouse
  • Place of Presentation: クロアチア、ザグレブ
  • Year and Date: 2008-09-06
• [Presentation] Polycomb group proteins Ring1A/B are functionally linked to the coretranscriptional regulatory circuitry to maintain ES cell identity (2008)
  • Author(s): 古関明彦
  • Organizer: Shanghai Cancer Institute
  • Place of Presentation: 中国、上海
  • Year and Date: 2008-07-03