Organization
Undergraduate School School of Agriculture Professor
Title
Professor
External link
Degree
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博士（農学） ( 1999.3 東京大学 )
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修士（農学） ( 東京大学 )
Research Interests
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DNA methylation
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Non-coding RNA
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Epigenomic engineering
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Epigenetics
Research Areas
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Environmental science/Agricultural science / Plant genetics and breeding / 農学
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Life sciences / Veterinary medicine / 畜産学・獣医学
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Life sciences / Veterinary medicine / 応用動物科学
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Life sciences / Genetics / 生物系
Education
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The University of Tokyo Graduate School of Agriculture and Life Sciences Faculty of Animal Resource Sciences
1996.4 - 1999.3
Country/Region： Japan
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The University of Tokyo Graduate School of Agriculture and Life Sciences Faculty of Animal Resource Sciences
1994.4 - 1996.3
Country/Region： Japan
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The University of Tokyo Faculty of Agriculture
- 1994.3
Country/Region： Japan
Research History
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明治大学農学部生命科学科 教授
2019.4
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Meiji University Associate Professor
2014.4 - 2019.3
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Meiji University Senior Assistant Professor
2011.4 - 2014.3
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Research Associate Assistant Professor (non-tenured)
1999.8 - 2011.3
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JSPS Special researcher of the Japan Society for the Promotion of Science Research Fellow
1999.4 - 1999.7
Professional Memberships
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日本畜産学会
2016.11
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日本下垂体研究会
2014.8
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日本農芸化学会
2011.9
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日本エピジェネティクス研究会
2007.4
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日本繁殖生物学会
1999.4
Committee Memberships
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日本繁殖生物学会 評議委員
2020.4
Committee type：Academic society
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日本繁殖生物学会 編集委員会
2015.4
Committee type：Academic society
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日本繁殖生物学会 男女共同参画委員会
2011.4
Committee type：Academic society
Papers
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Epigenome editing-mediated restoration of FBN1 expression by demethylation of CpG island shore in porcine fibroblasts. International journal
Rio Miyadai, Shiori Hinata, Yuya Amemiya, Satori Shigematsu, Kazuhiro Umeyama, Hiroshi Nagashima, Kenji Yamatoya, Jun Ohgane
Biochemistry and biophysics reports 42 101973 - 101973 2025.6
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Epigenome editing revealed the role of DNA methylation of T-DMR/CpG island shore on Runx2 transcription. International journal
Yutaro Kawa, Miyuki Shindo, Jun Ohgane, Masafumi Inui
Biochemistry and biophysics reports 38 101733 - 101733 2024.7
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Phenotypic features of genetically modified DMD-XKOXWT pigs. International journal
Kazutoshi Okamoto, Hitomi Matsunari, Kazuaki Nakano, Kazuhiro Umeyama, Koki Hasegawa, Ayuko Uchikura, Shuko Takayanagi, Masahito Watanabe, Jun Ohgane, Michael Stirm, Mayuko Kurome, Nikolai Klymiuk, Masaki Nagaya, Eckhard Wolf, Hiroshi Nagashima
Regenerative therapy 24 451 - 458 2023.12
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Genetically engineered animal models for Marfan syndrome: challenges associated with the generation of pig models for diseases caused by haploinsufficiency.
Naomi Jack, Tomoyuki Muto, Keigo Iemitsu, Tamaki Watanabe, Kazuhiro Umeyama, Jun Ohgane, Hiroshi Nagashima
The Journal of reproduction and development 68 ( 4 ) 233 - 237 2022.8
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Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells. International journal
Wenlong Wang, Tomohiro Ito, Satoshi Otsuka, Hiroko Nansai, Kuniya Abe, Yoichi Nakao, Jun Ohgane, Minoru Yoneda, Hideko Sone
Toxicology in vitro : an international journal published in association with BIBRA 75 105174 - 105174 2021.9
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DNA methylation ambiguity in the Fibrillin-1 (FBN1) CpG island shore possibly involved in Marfan syndrome. Reviewed International journal
Yoshikazu Arai, Kazuhiro Umeyama, Natsumi Okazaki, Kazuaki Nakano, Koichiro Nishino, Hiroshi Nagashima, Jun Ohgane
Sci Rep 10 ( 1 ) 5287 - 5287 2020.3
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Complete chloroplast genome sequence and phylogenetic analysis of wasabi (Eutrema japonicum) and its relatives. Reviewed International journal
Natsuko Haga, Masaaki Kobayashi, Nana Michiki, Tomoyuki Takano, Fujio Baba, Keiko Kobayashi, Hajime Ohyanagi, Jun Ohgane, Kentaro Yano, Kyoko Yamane
Sci Rep 9 ( 1 ) 14377 - 14377 2019.10
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Evidence of exposure to chemicals and heavy metals during pregnancy in Japanese women Reviewed
Ryo Maekawa, Rie Ito, Yusuke Iwasaki, Koichi Saito, Kazuhiko Akutsu, Satoshi Takatori, Rie Ishii, Fumio Kondo, Yoshikazu Arai, Jun Ohgane, Kunio Shiota, Tsunehisa Makino, Norihiro Sugino
Reproductive Medicine and Biology 16 ( 4 ) 337 - 348 2017.10
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Establishment of DNA methylation patterns of the Fibrillin1 (FBN1) gene in porcine embryos and tissues Reviewed
Yoshikazu Arai, Kazuhiro Umeyama, Kenta Takeuchi, Natsumi Okazaki, Naomi Hichiwa, Sayaka Yashima, Kazuaki Nakano, Hiroshi Nagashima, Jun Ohgane
JOURNAL OF REPRODUCTION AND DEVELOPMENT 63 ( 2 ) 157 - 165 2017.4
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Involvement of DNA methylation in regulating rat Prop1 gene expression during pituitary organogenesis. Reviewed International journal
Hiroto Nishihara, Saishu Yoshida, Naoko Kanno, Naoto Nishimura, Hiroki Ueharu, Jun Ohgane, Takako Kato, Yukio Kato
J Reprod Dev 63 ( 1 ) 37 - 44 2017.2
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Ultra-Deep Bisulfite Sequencing to Detect Specific DNA Methylation Patterns of Minor Cell Types in Heterogeneous Cell Populations: An Example of the Pituitary Tissue Reviewed
Yoshikazu Arai, Hisho Fukukawa, Takanori Atozi, Shoma Matsumoto, Yutaka Hanazono, Hiroshi Nagashima, Jun Ohgane
PLOS ONE 11 ( 1 ) e0146498 2016.1
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An epigenetic regulatory element of the Nodal gene in the mouse and human genomes. Reviewed International journal
Daisuke Arai, Koji Hayakawa, Jun Ohgane, Mitsuko Hirosawa, Yoichi Nakao, Satoshi Tanaka, Kunio Shiota
Mech Dev 136 143 - 154 2015.5
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Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells Reviewed
Yoshikazu Arai, Koji Hayakawa, Daisuke Arai, Rie Ito, Yusuke Iwasaki, Koichi Saito, Kazuhiko Akutsu, Satoshi Takatori, Rie Ishii, Rumiko Hayashi, Shun-Ichiro Izumi, Norihiro Sugino, Fumio Kondo, Masakazu Horie, Hiroyuki Nakazawa, Tsunehisa Makino, Mitsuko Hirosawa, Kunio Shiota, Jun Ohgane
BIOMED RESEARCH INTERNATIONAL 2015 ( 876047 ) 2015
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DNA methylation profiles provide a viable index for porcine pluripotent stem cells Reviewed
Yoshikazu Arai, Jun Ohgane, Shuh-Hei Fujishiro, Kazuaki Nakano, Hitomi Matsunari, Masahito Watanabe, Kazuhiro Umeyama, Dai Azuma, Naomi Uchida, Nozomu Sakamoto, Tomohiro Makino, Shintaro Yagi, Kunio Shiota, Yutaka Hanazono, Hiroshi Nagashima
Genesis 51 ( 11 ) 763 - 776 2013.11
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Oocyte-specific linker histone H1foo is an epigenomic modulator that decondenses chromatin and impairs pluripotency Reviewed
Koji Hayakawa, Jun Ohgane, Satoshi Tanaka, Shintaro Yagi, Kunio Shiota
EPIGENETICS 7 ( 9 ) 1029 - 1036 2012.9
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Bridging sequence diversity and tissue-specific expression by DNA methylation in genes of the mouse prolactin superfamily Reviewed
Koji Hayakawa, Momo O. Nakanishi, Jun Ohgane, Satoshi Tanaka, Mitsuko Hirosawa, Michael J. Soares, Shintaro Yagi, Kunio Shiota
MAMMALIAN GENOME 23 ( 5-6 ) 336 - 345 2012.6
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Disease-dependent differently methylated regions (D-DMRs) of DNA are enriched on the X chromosome in uterine leiomyoma. Reviewed International journal
Ryo Maekawa, Shintaro Yagi, Jun Ohgane, Yoshiaki Yamagata, Hiromi Asada, Isao Tamura, Norihiro Sugino, Kunio Shiota
J Reprod Dev Vol. 57 ( 5 ) 604 - 612 2011.10
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Epigenetic assessment of environmental chemicals detected in maternal peripheral and cord blood samples Reviewed
Yoshikazu Arai, Jun Ohgane, Shintaro Yagi, Rie Ito, Yusuke Iwasaki, Koichi Saito, Kazuhiko Akutsu, Satoshi Takatori, Rie Ishii, Rumiko Hayashi, Shun-Ichiro Izumi, Norihiro Sugino, Fumio Kondo, Masakazu Horie, Hiroyuki Nakazawa, Tsunehisa Makino, Kunio Shiota
Journal of Reproduction and Development 57 ( 4 ) 507 - 517 2011
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Enrichment of short interspersed transposable elements to embryonic stem cell-specific hypomethylated gene regions Reviewed
Hiroki Muramoto, Shintaro Yagi, Keiji Hirabayashi, Shinya Sato, Jun Ohgane, Satoshi Tanaka, Kunio Shiota
GENES TO CELLS 15 ( 8 ) 855 - 865 2010.8
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Genome-wide DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) residing in mouse pluripotent stem cells Reviewed
Shinya Sato, Shintaro Yagi, Yoshikazu Arai, Keiji Hirabayashi, Naoko Hattori, Misa Iwatani, Keisuke Okita, Jun Ohgane, Satoshi Tanaka, Teruhiko Wakayama, Shinya Yamanaka, Kunio Shiota
GENES TO CELLS 15 ( 6 ) 607 - 618 2010.6
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エピジェネティック調節 Invited
高杉征樹,大鐘潤,塩田邦郎
日本臨床 Vol.68 307 - 312 2010.2
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Establishment of trophoblast stem cell lines from somatic cell nuclear-transferred embryos Reviewed
Mayumi Oda, Satoshi Tanaka, Yukiko Yamazaki, Hiroshi Ohta, Misa Iwatani, Masako Suzuki, Jun Ohgane, Naka Hattori, Ryuzo Yanagimachi, Teruhiko Wakayama, Kunio Shiota
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106 ( 38 ) 16293 - 16297 2009.9
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Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus Reviewed
Koji Sato, Hideki Fukata, Yasushi Kogo, Jun Ohgane, Kunio Shiota, Chisato Mori
Endocrine Journal 56 ( 1 ) 131 - 139 2009
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Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development Invited Reviewed
Kohta Ikegami, Jun Ohgane, Satoshi Tanaka, Shintaro Yagi, Kunio Shiota
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY 53 ( 2-3 ) 203 - 214 2009
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DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression Reviewed
Shintaro Yagi, Keiji Hirabayashi, Shinya Sato, Wei Li, Yoko Takahashi, Tsutomu Hirakawa, Guoying Wu, Naoko Hattori, Naka Hattori, Jun Ohgane, Satoshi Tanaka, X. Shirley Liu, Kunio Shiota
GENOME RESEARCH 18 ( 12 ) 1969 - 1978 2008.12
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Potential link between estrogen receptor-alpha gene hypomethylation and uterine fibroid formation Reviewed
Hiromi Asada, Yoshiaki Yamagata, Toshiaki Taketani, Aki Matsuoka, Hiroshi Tamura, Naoko Hattori, Jun Ohgane, Naka Hattori, Kunio Shiota, Norihiro Sugino
MOLECULAR HUMAN REPRODUCTION 14 ( 9 ) 539 - 545 2008.9
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Epigenetics: The DNA methylation profile of tissue-dependent and differentially methylated regions in cells Invited Reviewed
J. Ohgane, S. Yagi, K. Shiota
PLACENTA 29 S29 - S35 2008.3
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Sequential changes in genome-wide DNA methylation status during adipocyte differentiation Reviewed
Hideki Sakamoto, Yasushi Kogo, Jun Ohgane, Naka Hattori, Shintaro Yagi, Satoshi Tanaka, Kunio Shiota
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 366 ( 2 ) 360 - 366 2008.2
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細胞特異的DNAメチル化プロフィール Invited
大鐘潤,ほか2名
蛋白質核酸酵素 Vol.52 2177 - 2182 2007.12
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DNA methylation errors in cloned mice disappear with advancement of aging Reviewed
Sho Senda, Teruhiko Wakayama, Yoshikazu Arai, Yukiko Yamazaki, Jun Ohgane, Satoshi Tanaka, Naka Hattori, Ryuzo Yanagimachi, Kunio Shiota
Cloning and Stem Cells 9 ( 3 ) 293 - 302 2007.9
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Epigenetic regulation of Nanog gene in embryonic stem and trophoblast stem cells Reviewed
Naoko Hattori, Yuko Imao, Koichiro Nishino, Naka Hattori, Jun Ohgane, Shintaro Yagi, Satoshi Tanaka, Kunio Shiota
GENES TO CELLS 12 ( 3 ) 387 - 396 2007.3
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Neonatal exposure to diethylstilbestrol alters the expression of DNA methyltransferases and methylation of genomic DNA in the epididymis of mice Reviewed International journal
Koji Sato, Hideki Fukata, Yasushi Kogo, Jun Ohgane, Kunio Shiota, Chisato Mori
Endocr. J Vol.53 ( No.3 ) 331 - 337 2006.6
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Methylation in embryonic stem cells in vitro Invited Reviewed International journal
Methods Mol. Biol Vol.329 421 - 445 2006.2
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発生・分化とエピジェネティクス Invited
岩谷美沙,大鐘潤,塩田邦郎
ゲノム医学 Vol.5 ( No.5 ) 25 - 30 2005.9
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Analysis of tissue-specific DNA methylation during development Invited Reviewed International journal
Methods Mol. Biol Vol.289 371 - 382 2004.10
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Non-coding RNA directed DNA demethylation of Sphk1 CpG island Reviewed
T Imamura, S Yamamoto, J Ohgane, N Hattori, S Tanaka, K Shiota
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 322 ( 2 ) 593 - 600 2004.9
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Skewed X-inactivation in cloned mice Reviewed
S Senda, T Wakayama, Y Yamazaki, J Ohgane, N Hattori, S Tanaka, R Yanagimachi, K Shiota
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 321 ( 1 ) 38 - 44 2004.8
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Different molecular mechanisms underlie placental overgrowth phenotypes caused by interspecies hybridization, cloning, and Esx1 mutation Reviewed
U Singh, LE Fohn, T Wakayama, J Ohgane, C Steinhoff, B Lipkowitz, R Schulz, A Orth, HH Ropers, RR Behringer, S Tanaka, K Shiota, R Yanagimachi, UA Nuber, R Fundele
DEVELOPMENTAL DYNAMICS 230 ( 1 ) 149 - 164 2004.5
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Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells Reviewed
N Hattori, K Nishino, YG Ko, N Hattori, J Ohgane, S Tanaka, K Shiota
JOURNAL OF BIOLOGICAL CHEMISTRY 279 ( 17 ) 17063 - 17069 2004.4
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The Sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice Reviewed
J Ohgane, T Wakayama, S Senda, Y Yamazaki, K Inoue, A Ogura, J Marh, S Tanaka, R Yanagimachi, K Shiota
GENES TO CELLS 9 ( 3 ) 253 - 260 2004.3
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Genome-wide analysis of DNA methylation status of CpG islands in embryoid bodies, teratomas, and fetuses Reviewed
M Kremenskoy, Y Kremenska, J Ohgane, N Hattori, S Tanaka, K Hashizume, K Shiota
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 311 ( 4 ) 884 - 890 2003.11
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DNAメチル化からみたほ乳類ゲノムの進化とクローン動物 Invited
高畑尚之,中込弥男,森脇和郎,大鐘潤,塩田邦郎
生物の科学 遺伝 別冊No15「遺伝学はゲノム情報でどう変わるか」 ( No15 ) 2002.11
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Epigenetic marks by DNA methylation specific to stem, germ and somatic cells in mice Reviewed
K Shiota, Y Kogo, J Ohgane, T Imamura, A Urano, K Nishino, S Tanaka, N Hattori
GENES TO CELLS 7 ( 9 ) 961 - 969 2002.9
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Differentiation of trophoblast lineage is associated with DNA methylation and demethylation Reviewed
J Ohgane, N Hattori, M Oda, S Tanaka, K Shiota
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 290 ( 2 ) 701 - 706 2002.1
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Placentomegaly in cloned mouse concepti caused by expansion of the spongiotrophoblast layer Reviewed International journal
S Tanaka, M Oda, Y Toyoshima, T Wakayama, M Tanaka, N Yoshida, N Hattori, J Ohgane, R Yanagimachi, K Shiota
Biol. Reprod Vol.65 ( No.6 ) 1813 - 1821 2001.12
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CpG island of rat sphingosine kinase-1 gene: tissue-dependent DNA methylation status and multiple alternative first exons Reviewed
T Imamura, J Ohgane, S Ito, T Ogawa, N Hattori, S Tanaka, K Shiota
GENOMICS 76 ( 1-3 ) 117 - 125 2001.8
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DNA methylation regulates placental lactogen I gene expression Reviewed
JH Cho, H Kimura, T Minami, J Ohgane, N Hattori, S Tanaka, K Shiota
ENDOCRINOLOGY 142 ( 8 ) 3389 - 3396 2001.8
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Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate Reviewed International journal
JL Yan, S Tanaka, M Oda, T Makino, J Ohgane, K Shiota
Dev. Biol Vol.235 ( No.2 ) 422 - 432 2001.7
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DNA methylation variation in cloned mice Reviewed
J Ohgane, T Wakayama, Y Kogo, S Senda, N Hattori, S Tanaka, R Yanagimachi, K Shiota
GENESIS 30 ( 2 ) 45 - 50 2001.6
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Analysis of CpG islands of trophoblast giant cells by restriction landmark genomic scanning Reviewed
J Ohgane, JI Aikawa, A Ogura, N Hattori, T Ogawa, K Shiota
DEVELOPMENTAL GENETICS 22 ( 2 ) 132 - 140 1998
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Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy Reviewed International journal
J Aikawa, S IkedaNaiki, J Ohgane, KS Min, T Imamura, K Sasai, K Shiota, T Ogawa
Biochim. Biophys. Acta Vol.1353 ( No.3 ) 266 - 276 1997.9
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Nutritional regulation of gene expression of insulin-like growth factor-binding proteins and the acid-labile subunit in various tissues of rats Reviewed
A Takenaka, M Mori, S Yamada, J Ohgane, SI Takahashi, T Noguchi
JOURNAL OF ENDOCRINOLOGY 150 ( 1 ) 33 - 41 1996.7
Books
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「組織特異的メチル化と体細胞核移植クローン」 『エピジェネティクス』
編者:佐々木裕之 共著者:大鐘潤,ほか2名（ Role： Joint author）
シュプリンガー東京 2004.4
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「生殖とエピジェネティクス –胎盤栄養膜細胞ゲノムDNAの組織特異的メチル化」 『生殖ジェネティクス』
鈴木秋悦,塩田邦郎（ Role： Joint author）
メジカルビュー社 1999.11
MISC
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エピジェネティクス
服部奈緒子, 大鐘潤, 塩田邦郎
化学と生物 44 841 - 850 2006
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組織特異的DNAメチル化と体細胞核移植クローニング
大鐘潤, 小田真由美, 塩田邦郎
エピジェネティックス、シュプリンガーフェアラーク東京 147 - 1154 2004
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Effect of benzo(a)pyrene on placentation.
J Tomikawa, JL Yan, J Ohgane, N Hattori, T Makino, S Tanaka, K Shiota
BIOLOGY OF REPRODUCTION 66 199 - 199 2002
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Mouse trophoblast cells are resistant to AhR ligand
J Tomikawa, JL Yan, J Ohgane, N Hattori, S Tanaka, K Shiota
MOLECULAR BIOLOGY OF THE CELL 12 504A - 504A 2001.11
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Placentomegaly in cloned mice caused by expansion of spongiotrophoblast layer.
S Tanaka, M Oda, Y Toyoshima, T Wakayama, M Tanaka, N Yoshida, N Hattori, J Ohgane, R Yanagimachi, K Shiota
BIOLOGY OF REPRODUCTION 64 171 - 171 2001
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生殖とエピジェネティックス、胎盤栄養膜細胞ゲノムDNAの組織特異的メチル化
大鐘潤, 塩田邦郎
Modern Reproductive Medicine、生殖とGenetics 3 34 - 42 1999
Research Projects
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Generation of pigs for human transplantation and establishment of a system to assess their suitability for human use.
Grant number：24K02513 2024.4 - 2027.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Grant amount：\18590000 （ Direct Cost: \14300000 、 Indirect Cost：\4290000 ）
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Epigenetic fluctuation associated with onset and severity of haploinsufficient dominant diseases
Grant number：21H04755 2021.4 - 2024.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Ohgane Jun
Authorship：Principal investigator
Grant amount：\51840000 （ Direct Cost: \42120000 、 Indirect Cost：\9720000 ）
To generate mice that are heterozygous for the porcine CpG shore normal allele and the mouse null allele for the FBN1 gene locus, we established ES cells with the above genotype and are planning to generate the heterozygous mice. Furthermore, promoter assays of FBN1 revealed that the FBN1 CpG shores exhibiting fluctuations in DNA methylation, function as a proximal enhancer. Furthermore, we found that the promoter activities of the CpG island and shore are suppressed by DNA methylation. Regarding RUNX2, we introduced an epigenome editing vector that induces DNA hypermethylation into stem cells that can differentiate into chondrocytes, and demonstrated that it is possible to induce DNA hypermethylation in the Runx2 promoter.
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Elucidation of etiology and phenotypic control in a porcine autosomal dominant genetic disease model
Grant number：15H02480 2015.4 - 2019.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Nagashima Hiroshi
Authorship：Coinvestigator(s)
Marfan syndrome (MFS) is an autosomal dominant genetic disease. We established a porcine model for MFS by introducing a mutation (Glu433AsnfsX98) in the Fibrillin1 (FBN1) gene. We also identified a single nucleotide polymorphism (SNP) in FBN1 promotor CpG shore in a pig. Using the offspring (F1) obtained by mating of MFS females and a SNP-identified male, relationship between the methylation status of FBN1 CpG shore and the expression level of FBN1 was identified. Our results suggested that epigenetic modification of the responsible gene expression is involved in the etiology of MFS exhibiting haploinsufficiency.
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Detection of chemical substances with epigenetic activity to protect environmental risk by the adverse outcome pathway approach
Grant number：15H01749 2015.4 - 2019.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Sone Hideko, Nansai Hiroko, Kondo Masayo, Suzuki Shinnosuke, Otsuka Satoshi
Authorship：Coinvestigator(s)
We developed a method to visually detect DNA methylation and histone modification as an index of epigenetic status using pluripotent stem cells like mouse ES and human iPS cells. Using this engineered cell lines, one hundred and thirty-five chemical substances were analyzed. Further epigenetic toxicity was detected by examining DNA methylation variation in the promoter region of the disease causing gene in detail by analysis of specific DNA sequences. The effect of irradiation on the differentiation of human iPS cells into retinal ganglion cells was also investigated. Further we have developed a method that can detect differences in epigenetic status during differentiation derived from undifferentiated stem cells. These results suggest that the rapid detection of epigenetic activity using pluripotent stem cells can detect initial events of exposures to chemicals and environmental factors and then predict the later effects.
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Comprehensive understanding of favorable trait of porcine meat and unfavorable chronic diseases in human on the basis of epigenomic engineering
2013.4 - 2015.3
Authorship：Principal investigator
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機能性非コードRNAによるエピゲノム改変を利用した有用細胞および病態モデル動物の作出
2013.4 - 2015.3
Authorship：Principal investigator
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Optimization of epigenomic modification with regulatory RNAs considering the presence of endogenous non-coding RNAs
Grant number：22710181 2010.4 - 2012.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
OHGANE Jun
Authorship：Principal investigator
Recent accumulating evidences have indicated that various non-coding RNAs(ncRNAs) are involved in region-specific epigenetic regulations. Since many endogenous ncRNAs show tissue/cell-type-dependent expression patterns, it is important to reveal the relationships between tissue/cell-type-dependent expression and epigenetic regulations. Our data indicated that many genes had ncRNAs within promoter regions of tissu/cell-type-specific genes whose DNA methylation status changed by deficiency of ncRNA-related enzymes. The Sall4 gene, which is crucial for stemness of embryonic stem(ES) cells, had an endogenous antisense ncRNA(ASncRNA) overlapping with the promoter region of the protein-coding Sall4 gene. The Sall4 ASncRNA regulated DNA methylation status of the Sall4 promoter independent of double-strand RNA synthesis by Dicer. An ectopic overexpression of the ASncRNA in fibroblast cells resulted DNA demethylation of the Sall4 promoter region. The Sall4 ASncRNA was proven indispensable for maintenance of unmethylated and activated status in ES cells by shRNA knockdown of the endogenous ASncRNA. Our data also indicated that oocyte-specific histone and environmental chemicals were involved in epigenetic regulations. In conclusion, we could identify many ASncRNAs that regulate DNA methylation status in a target-specific manner, and these ASncRNAs are thought as useful for epigenome modification to establish epigenome-related disease model animals and cells.
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Analysis of Sex-dependent Epigenome
Grant number：21221008 2009.5 - 2014.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S)
SHIOTA Kunio, YAGI Shintaro, OHGANE Jun, NAKAYAMA Hiroyuki, TANEMURA Kentaro, YAMANOUCHI Keitaro, TANAKA Satoshi, KIKUSUI Takefumi, YAMANOUCHI Keitaro, YAGI Shintaro, TANEMURA Kentaro, HIROSAWA Mitsuko
Grant amount：\208390000 （ Direct Cost: \160300000 、 Indirect Cost：\48090000 ）
What is known about the biology of sexual differences is that there are striking differences in the biological functions that can lead to human and animal diseases. Epigenetic systems are recognized as memory systems for inheritable gene functions. DNA methylation plays a role the main epigenetic regulation mechanism in mammals. A unique feature of the mammalian genome is that there are numerous tissue-dependent and differentially methylated regions (T-DMRs), which include genes and their regulatory elements. We have developed D-REAM, a genome-wide DNA methylation analysis method using a genome tiling array, for T-DMRs profiling with restriction tag-mediated amplification. This research project highlights the epigenome of tissues and cells in male and female respectively. We found that there are T-DMRs that are differentially methylated between male and female animals, other than those found in the sex chromosomes and the genomic regions related to sexual organs development.
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Epigenetics on transdifferentiation of ES cells toward TS cells
Grant number：21248039 2009.4 - 2011.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
TANAKA Satoshi, OHGANE Jun, SHIOTA Kunio, FURUE Miho
Authorship：Coinvestigator(s)
To elucidate if mESCs pass through TSC-like and/or EpiSC-like state during the process of BMP4-induced transdifferentiation, we investigated nature of intermediate cell population in the transdifferentiation process. Immunohistochemistry revealed the presence of TSC-like cell colonies only in the BMP4-treated cultures. We then subcultured BMP4-treated mESCs under the conditions for maintenance of TSCs, and consequently obtained a cell line. DNA microarray analysis revealed that the gene expression profile of then new cell line is more similar to that of EpiSCs compared to mTSCs and mESCs. These results suggest that BMP4-treated mESCs may transdifferentiate to TCs through two independent pathways. One is the pathway through mTSC-like state and the other through mEpiSC-like state.
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Epigenome formation and cellular differentiation in mouse embryogenesis
Grant number：20062003 2008.4 - 2012.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas
TANAKA Satoshi, OHGANE Jun, SHIOTA Kunio
Authorship：Coinvestigator(s)
We analyzed DNA methylation profiles of mouse embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), and compared those with DNA methylation profiles of some somatic tissues. Consequently, we identified genomic regions that show methylation statuses specific to each stem cell line. By using DNA methylation profile as one of the indexes, we revealed that the TSCs derived from blastocysts produced by somatic cell nuclear transfer are indistinguishable from normal TSCs. We also showed that trophoblast-specific DNA methylation occurs after the segregation of the trophectoderm and inner cell mass in the mouse periimplantation embryo.
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生研センター 新技術・新分野創出のための基礎研究推進事業 「DNAメチル化情報の解析による動物ゲノムの高度利用」分担研究者
1999.4 - 2003.3
Authorship：Coinvestigator(s) Grant type：Competitive
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学術振興会特別研究員（DC2-PD）「胎盤ゲノムCpGアイランドの解析：細胞分化とクローン動物の分子基盤」研究代表者
Grant number：98J04734 1998.4 - 1999.7
日本学術振興会 科学研究費助成事業 特別研究員奨励費
大鐘 潤
Authorship：Principal investigator Grant type：Competitive
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