Establishment of the chromatin state in gonadal development

• Project/Area Number: 18K06926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Yuko Katoh-fukui 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, (非)研究員 (50342639)
• Co-Investigator(Kenkyū-buntansha): 竹内 隆 鳥取大学, 医学部, 教授 (70197268)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: クロマチン / 生殖腺 / 分化 / マウス / 発生 / 転写制御 / 性分化疾患 / Polycomb / Jarid2 / 遺伝子制御 / 哺乳類

Outline of Final Research Achievements

Dynamic chromatin structural transformation occurs in the differentiated cell nucleus. In this study, we focused on the Polycomb Group (PcG) member, Cbx2 and the chromatin component Jarid2 (Jumonji), which is known to associate with PcG in ES cells. In order to verify the Jarid2 flox allele, we deleted floxed exon three regions by using germ-line active Cre. The obtained Jarid2 deficient embryo confirmed edema, septal defect of the heart, and hypoplasia of the liver, similar to the phenotypes observed in previously reported gene-trap mice. In addition, we found an unreported dysplasia of the urogenital regions and retinal coloboma. Furthermore, mutation analysis of these factors in disorders of sex development (DSD) was performed.

Academic Significance and Societal Importance of the Research Achievements

発生中の多様な時期に、多様な組織で機能を果たすクロマチン構成因子のより詳細な解析のために、Jarid2 flox alleleマウスを用いた組織特異的機能解析が可能であることが明らかになった。DSDのみならず様々な小児疾患原因因子あるいはリスク因子としてクロマチン構成因子変異が検討されるべきであることを示した。

Research Products

• [Journal Article] NDNF variants are rare in patients with congenital hypogonadotropic hypogonadism (2021)
  • Author(s): Tamaoka Satoshi、Suzuki Erina、Hattori Atsushi、Ogata Tsutomu、Fukami Maki、Katoh-Fukui Yuko
  • Journal Title: Human Genome Variation Volume: 8 Issue: 1 Pages: 5-5
  • DOI: 10.1038/s41439-021-00137-x
  • Peer Reviewed / Open Access
• [Journal Article] Nonsense-associated altered splicing of MAP3K1 in two siblings with 46,XY disorders of sex development. (2020)
  • Author(s): Igarashi M, Masunaga Y, Hasegawa Y, Kinjo K, Miyado M, Saitsu H, Kato-Fukui Y, Horikawa R, Okubo Y, Ogata T and Fukami M.
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 17375-17375
  • DOI: 10.1038/s41598-020-74405-1
  • Peer Reviewed / Open Access
• [Journal Article] SOX9 is colocalized with paraspeckle protein NONO in cultured murine sertoli cells and features structural characteristics of intrinsically disordered proteins (2020)
  • Author(s): Akiba Kazuhisa、Narumi Satoshi、Nishimura Riko、Kato‐Fukui Yuko、Takada Shuji、Hasegawa Yukihiro、Fukami Maki
  • Journal Title: Molecular Reproduction and Development Volume: 87 Issue: 11 Pages: 1124-1125
  • DOI: 10.1002/mrd.23425
  • Peer Reviewed / Open Access
• [Journal Article] Frequency of Common Copy-Number Variations at 15q11.2q13 in Sperm of Healthy Men (2019)
  • Author(s): 1.Kinoshita T, Mikami M, Ayabe T, Matsubara K, Ono H, Ohki K, Fukami M＊, Katoh-Fukui Y
  • Journal Title: Cytogenet Genome Res. Volume: 159 Issue: 2 Pages: 66-73
  • DOI: 10.1159/000503267
  • Peer Reviewed
• [Journal Article] Transient multifocal genomic crisis creating chromothriptic and non-chromothriptic rearrangements in prezygotic testicular germ cells. (2019)
  • Author(s): Hattori A, Okamura K, Terada Y, Tanaka R, Katoh-Fukui Y, Matsubara Y, Matsubara K, Kagami M, Horikawa R, Fukami M
  • Journal Title: BMC Med Genomics. Volume: 12 Issue: 1 Pages: 77-77
  • DOI: 10.1186/s12920-019-0526-3
  • Peer Reviewed / Open Access
• [Journal Article] A case of combined 21‐hydroxylase deficiency and CHARGE syndrome featuring micropenis and cryptorchidism (2019)
  • Author(s): Umino Satoko、Kitamura Miyuki、Katoh‐Fukui Yuko、Fukami Maki、Usui Takeshi、Yatsuga Shuichi、Koga Yasutoshi
  • Journal Title: Molecular Genetics & Genomic Medicine Volume: － Issue: 6
  • DOI: 10.1002/mgg3.730
  • Peer Reviewed
• [Journal Article] MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration (2019)
  • Author(s): Hamanaka K、Takata A、Uchiyama Y、Miyatake S、Miyake N、Mitsuhashi S、Iwama K、Fujita A、Imagawa E、Alkanaq AN、Koshimizu E、Azuma Y、Nakashima M、Mizuguchi T、Saitsu H、Wada Y、Minami S、Katoh-Fukui Y、Masunaga Y、Fukami M、Hasegawa T、Ogata T、Matsumoto N
  • Journal Title: Human Molecular Genetics Volume: 印刷中 Issue: 14 Pages: 2319-2329
  • DOI: 10.1093/hmg/ddz066
  • Peer Reviewed
• [Journal Article] WDR11 is another causative gene for coloboma, cardiac anomaly and growth retardation in 10q26 deletion syndrome (2019)
  • Author(s): Sutani Akito、Shima Hirohito、Hijikata Atsushi、Hosokawa Susumu、Katoh-Fukui Yuko、Takasawa Kei、Suzuki Erina、Doi Shozaburo、Shirai Tsuyoshi、Morio Tomohiro、Fukami Maki、Kashimada Kenichi
  • Journal Title: European Journal of Medical Genetics Volume: 印刷中 Issue: 1 Pages: 103626-103626
  • DOI: 10.1016/j.ejmg.2019.01.016
  • Peer Reviewed / Open Access
• [Journal Article] Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones (2019)
  • Author(s): Katoh-Fukui Yuko、Baba Takashi、Sato Tetsuya、Otake Hiroyuki、Nagakui-Noguchi Yuko、Shindo Miyuki、Suyama Mikita、Ohkawa Yasuyuki、Tsumura Hideki、Morohashi Ken-ichirou、Fukami Maki
  • Journal Title: Bone Volume: 120 Pages: 219-231
  • DOI: 10.1016/j.bone.2018.10.021
  • Peer Reviewed / Open Access
• [Journal Article] An unclassified variant of CHD7 activates a cryptic splice site in a patient with CHARGE syndrome (2018)
  • Author(s): Katoh-Fukui Yuko、Yatsuga Shuichi、Shima Hirohito、Hattori Atsushi、Nakamura Akie、Okamura Kohji、Yanagi Kumiko、Iso Manami、Kaname Tadashi、Matsubara Yoichi、Fukami Maki
  • Journal Title: Human Genome Variation Volume: 5 Issue: 1 Pages: 18006-18006
  • DOI: 10.1038/hgv.2018.6
  • Peer Reviewed / Open Access
• [Presentation] Cｂｘ2cterm/ctermマウスが出生後に示す多様な表現型 (2019)
  • Author(s): 福井由宇子，務台英樹，深見真紀
  • Organizer: 第42回日本分子生物学会年会 福岡
• [Presentation] Multifocal and multifaceted genomic crisis leading to highly complex chromosomal rearrangements in a boy with congenital disorders (2019)
  • Author(s): Atsushi Hattori, Kohji Okamura, Yumiko Terada, Rika Tanaka, Yuko Katoh-Fukui, Yoichi Matsubara, Keiko Matsubara, Masayo Kagami, Reiko Horikawa, and Maki Fukami
  • Organizer: The Pediatric Academic Societies Meeting, Baltimore, MD
  • Int'l Joint Research
• [Presentation] 健常日本人精子染色体におけるPWS領域微小欠失頻度と季節性 (2018)
  • Author(s): 木下貴裕、三上剛史、綾部匡之、松原圭子、小野ひろみ、福井由宇子、深見真紀
  • Organizer: 日本分子生物学会、横浜、