| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○招待 (推奨): |
| ○審査 (推奨): |
| ○カテゴリ (推奨): |
| ○共著種別 (推奨): |
| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 黒木 俊介
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| ○学籍番号 (推奨): |
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| 2. | 岡下 修己
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| 3. | (英) Baba Shoko (日) (読)
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| 4. | (英) Maeda Ryo (日) (読)
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| 5. | 宮脇 慎吾
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| 6. | 矢野 雅司 ([徳島大学.技術支援部])
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| ○学籍番号 (推奨): |
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| 7. | (英) Yamaguchi Miyoko (日) (読)
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| 8. | (英) Kitano Satsuki (日) (読)
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| 9. | (英) Miyachi Hitoshi (日) (読)
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| 10. | (英) Itoh Akihiro (日) (読)
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| 11. | (英) Yoshida Minoru (日) (読)
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| 12. | 立花 誠
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| ○学籍番号 (推奨): |
| [継承] |
| ○題名 (必須): | □ | (英) Rescuing the aberrant sex development of H3K9 demethylase Jmjd1a-deficient mice by modulating H3K9 methylation balance (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | 女性 (female)
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| 3. | (英) Gene Expression Regulation (日) (読)
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| 4. | (英) Genetic Loci (日) (読)
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| 5. | (英) Gonads (日) (読)
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| 6. | (英) Histone-Lysine N-Methyltransferase (日) (読)
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| 7. | (英) Histones (日) (読)
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| 8. | (英) Jumonji Domain-Containing Histone Demethylases (日) (読)
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| 9. | 男性 (male)
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| 10. | (英) Methylation (日) (読)
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| 11. | (英) Mice (日) (読)
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| 12. | (英) Mice, Inbred C57BL (日) (読)
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| 13. | ノックアウトマウス (knockout mice)
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| 14. | (英) SOX9 Transcription Factor (日) (読)
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| 15. | (英) Sequence Analysis, DNA (日) (読)
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| 16. | (英) Sex-Determining Region Y Protein (日) (読)
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| 17. | (英) Sexual Development (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | PLoS Genetics (Public Library of Science)
(pISSN: 1553-7390, eISSN: 1553-7404)
| ○ISSN (任意): | □ | 1553-7404
ISSN: 1553-7390
(pISSN: 1553-7390, eISSN: 1553-7404) Title: PLoS geneticsTitle(ISO): PLoS GenetPublisher: PLOS (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 13
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| ○号 (必須): | □ | 9
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| ○頁 (必須): | □ | e1007034 e1007034
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2017年 9月 26日 (平成 29年 9月 26日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1371/journal.pgen.1007034 (→Scopusで検索)
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| ○PMID (任意): | □ | 28949961 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): |
| ○Scopus (任意): | □ | 2-s2.0-85031322584
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| ○評価値 (任意): |
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| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1371/journal.pgen.1007034 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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