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エピジェネティックな仕組みによる遺伝子発現制御機構
同じDNA配列を持ちながら、皮膚の細胞と神経の細胞がまったく異なる性質を持つのはなぜでしょうか？その鍵を握るのがエピジェネティクスです。DNAの配列そのものを変えることなく、遺伝子の「読まれ方」を可逆的に制御するこの仕組みを通じて、細胞の分化や運命決定がどのように制御されるのかを、次世代シークエンサーによるゲノムワイド解析と組織学的解析を組み合わせながら明らかにしています。
不妊や発生異常の分子メカニズム
少子化が加速する現代社会において、不妊症の増加は深刻な課題です。私たちは生殖細胞から初期発生に至るまでの未知の分子メカニズムの解明に取り組んでいます。精子形成や初期胚においてエピジェネティックな制御がどのように機能するかを、次世代シークエンサーや超解像顕微鏡などの最先端技術を駆使して解析しています。
環境変化によるエピゲノム異常と細胞分化への影響
わずかな温度の上昇が、細胞の運命を変えうるとしたらどうでしょうか。私たちの研究から、生殖細胞のエピゲノムがほんのわずかな温度上昇によって異常をきたすこと（Kuroha et al., 2025）、そして生殖系列のエピゲノム異常が受精後の発生にまで影響を及ぼしうること（Tomizawa et al., 2018）が明らかになってきました。環境変化が生殖や発生に影響するという現象は、現代社会における健康や持続可能性への新たな視点を与えてくれます。
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Development dev.204239. (2025)
Abnormal H3K27me3 underlies degenerative spermatogonial stem cells in cryptorchid testis.
Kazushige Kuroha, Ivana Dočkal, Uroš Radović, Kuniko Nakajima, Ikue Hoshi, Shion Matsuda, Noriko Kojitani, Kazuyuki Ohbo, Shin-ichi Tomizawa
Gene Expr Patterns (2024) 54, 119383
表紙に選ばれました.
Spatial and temporal expression analysis of BMP signal modifiers, Smoc1 and Smoc2, from postnatal to adult developmental stages in the mouse testis.
M Ono, K Nakajima, S Tomizawa, T Shirakawa, I Okada, H Saitsu, N Matsumoto , K Ohbo
Development (2024) 151(18): dev202834
A non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis.
S. Tomizawa, R. Fellows, M. Ono, K.e Kuroha, I. Dockal, Y. Kobayashi, K. Minamizawa, K. Natsume, K. Nakajima, I. Hoshi,S. Matsuda, M. Seki, Y. Suzuki, K. Aoto, H. Saitsu, K. Ohbo
Asian Journal of Andrology (2024) 26, 1-7
A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia.
Shin-ichi Tomizawa*, Kazushige Kuroha*, Michio Ono, Kuniko Nakajima, Kazuyuki Ohbo
Clinical Epigenetics 13, Article number: 132 (2021)
Oxygen concentration affects de novo DNA methylation and transcription in in vitro cultured oocytes.
Florence Naillat, Heba Saadeh, Joanna Nowacka-Woszuk, Lenka Gahurova, Fatima Santos, Shin-ichi Tomizawa & Gavin Kelsey.
Development (2021) 148, dev194605.
Maintenance DNA methylation in pre-meiotic germ cells regulates meiotic prophase by facilitating homologous chromosome pairing.
Takada Y, Yaman-Deveci R, Shirakawa T, Shari J, Tomizawa S, Miura F, Ito T, Ono M, Nakajima K, Koseki Y, Shiotani F, Ishiguro K, Ohbo K, Koseki H.
Development (2021) 148 (8): dev196212.
Tsga8 is required for spermatid morphogenesis and male fertility in mice.
Kobayashi Y, Tomizawa S, Ono M, Kuroha K, Minamizawa K, Natsume K, Dizdarević S, Dočkal I, Tanaka H, Kawagoe T, Seki M, Suzuki Y, Ogonuki N, Inoue K, Matoba S, Anastassiadis K, Mizuki N, Ogura A, Ohbo K.
Dis Model Mech (2019) 12 (11): dmm040139.
Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice.
Nakajima K, Ono M, Radović U, Dizdarević S, Tomizawa SI, Kuroha K, Nagamatsu G, Hoshi I, Matsunaga R, Shirakawa T, Kurosawa T, Miyazaki Y, Seki M, Suzuki Y, Koseki H, Nakamura M, Suda T, Ohbo K.
Development 145 (2018)
Kmt2b conveys monovalent and bivalent H3K4me3 in spermatogonial stem cells at germline and embryonic promoters.
Tomizawa S, Kobayashi Y, Shirakawa T, Watanabe K, Mizoguchi K, Hoshi I, Nakajima K, Nakabayashi J, Singh S, Dahl A, Alexopoulou D, Seki M, Suzuki Y, Royo H, Peters AHFM, Anastassiadis K, Stewart AF, Ohbo K
Mol Cell Biol. 37(19): e00082-17 (2017)
EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.
Dong Y, Isono KI, Ohbo K, Endo TA, Ohara O, Maekawa M, Toyama Y, Ito C, Toshimori K, Helin K, Ogonuki N, Inoue K, Ogura A, Yamagata K, Kitabayashi I, Koseki H.
Epigenetics & Chromatin 10: 25-44 (2017)
Transcription and chromatin determinants of de novo DNA methylation timing in oocytes
Gahurova L*, Tomizawa S*, Smallwood SA, Stewart-Morgan KR, Saadeh H, Kim J, Andrews S, Chen T, Kelsey G *Contributed equally
GENES & DEVELOPMENT 29(23):2449-2462 (2015)
Dynamic changes in histone modifications precede de novo DNA methylation in oocytes
Kathleen R. Stewart, Lenka Veselovska, Jeesun Kim, Jiahao Huang, Heba Saadeh, Shin-ichi Tomizawa, Sébastien A. Smallwood, Taiping Chen, and Gavin Kelsey
Genome Biology 16: 209-215 (2015)
Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape.
Lenka Veselovska, Sebastien A. Smallwood, ... Shin-ichi Tomizawa4, Simon Andrews and Gavin Kelsey*
BioMol Concepts 6(1): 1–9 2015
Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming.
Kazuyuki Ohbo and Shin-ichi Tomizawa
BMC Genomics 16:624-40 2015
DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis.
Naoki Kubo, ……., Takayuki Shirakawa, Hidetoshi Sone, Yasuyuki Sato, Shin-ichi Tomizawa, Kazuyuki Ohbo
Biological Research. 48:48-62 2015
Inhibition of Rho-associated kinases disturbs the collective cell migration of stratified TE-10 cells.
Taro Mikami, Keiichiro Yoshida, Hajime Sawada, Michiyo Esaki, Kazunori Yasumura and Michio Ono
Dev Cell., 34: 1-12 2015
The RNA binding protein Nanos2 organizes a post-transcriptional buffering system to retain primitive state of mouse spermatogonial stem cells.
Zhou, Z., Shirakawa, T., Ohbo, K., Sada, A., Wu, Q., Hasegawa, K., Saba, R. and Saga, Y.
Curr. Pathobiol. Rep., 2:1-9 2014
Stem Cell Epigenetics: Insights from Studies on Embryonic, Induced Pluripotent, and Germline Stem Cells.
Shin-ichi Tomizawa, Takayuki Shirakawa, Kazuyuki Ohbo
Development, 140:3565-3576. 2013
An epigenetic checkpoint controls the transition from a stem cell pool to a progenitor cell state in mouse male germ cells.
Shirakawa T., Yaman-Deveci R., Tomizawa S., Kamizato Y., Nakajima K., at.,al.
Cell Biochem. Func 30(1), 33-40 2012
Plasmodium induced by SU6656, an Src family kinase inhibitor, is accompanied by a contractile ring defect.
Yoshida K, Ono M, Bito H, Mikami T, Sawada H
The International journal of developmental biology 56 867-875 2012
DNA methylation establishment during oocyte growth: mechanisms and significance.
Tomizawa S, Nowacka-Woszuk J, Kelsey G
Nature genetics 43 811-814 2011
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.
Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A, Sato S, Hata K, Andrews SR, Kelsey G
Development, 138:4207-4217. 2011
HP1γ links histone methylation marks to meiotic synapsis in mice.
Takada Y., Naruse C., Costa Y., Shirakawa S., Tachibana M., Sharif J., Kezuka-Shiotani F., Kakiuchi D., Masumoto H., Shinkai Y., Ohbo K., Peters A. H.F.M., Turner J. M.A., Asano M. and Koseki K.
Development 138 811-820 2011
Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes.
Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K, Kelsey G, Sasaki H
Science 332 848-852 2011.
Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.
Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H
Epigenetics & Chromatin 2:5, 2009.
The histone3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis.
Glaser S., Lubitz S., Loveland KL., Ohbo K., Robb L., Schwenk F., Seibler J., Roellig D, Kranz A., Anastassiadis K. and Stewart AF.
Mol Cell Biol. 26:8498-506. 2006.
A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages.
Nagamatsu G, Ohmura M, Mizukami T, Hamaguchi I, Hirabayashi S, Yoshida S, Hata Y, Suda T, and Ohbo K.
Development, 133:1495-1505. 2006.
The first round of mouse spermatogenesis lacks the stem cell stage.
Yoshida S, Sukeno, M, Nakagawa T, Ohbo K, Nagamatsu G, Suda T. and Nabeshima Y-I.
富澤 信一
尾野 道男
黒羽 一誠
中島 久仁子
星 郁栄
麹谷 典子
林 亜葵
南澤 恵佑
松田 菜那
柏木 悠我
- 博士課程：白川峰征、小林裕貴
- 修士課程：松田志穏、Monika Šafhauzer、Ivana Dočkal、Selma Dizdarevic、夏目幸治、溝口敬太、Uroš Radović
- 卒研生：前川友紀、渡邉久美子、杉山宗太郎
- リサクラ：熊谷凌、藤澤賢太郎
- 研究テーマ： エピジェネティクスによる細胞分化や運命決定制御機構の解析
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アウトライン
| 教室名 | 横浜市立大学医学部組織学 |
|---|---|
| 住所 | 横浜市金沢区福浦３−９ |
| 教授 | ---- |
| 専門 | 解剖学、組織学、エピジェネティクス、生殖細胞、細胞生物学など |
| 技術 | 電子顕微鏡、超解像度顕微鏡、遺伝子解析など |
| 教室員 | 教員３名、職員等４名 |