| Item type |
文献 / Documents(1) |
| 公開日 |
2020-03-13 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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|
識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pgen.1007034 |
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言語 |
ja |
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|
関連名称 |
10.1371/journal.pgen.1007034 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Rescuing the aberrant sex development of H3K9 demethylase Jmjd1a-deficient mice by modulating H3K9 methylation balance |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Tuning of Sry expression by H3K9 methylation and demethylation |
|
言語 |
en |
| 著者 |
黒木, 俊介
岡下, 修己
ババ, ショウコ
マエダ, リョウ
宮脇, 慎吾
矢野, 雅司
ヤマグチ, ミヨコ
キタノ, サツキ
ミヤチ, ヒトシ
イトウ, アキヒト
ヨシダ, ミノル
立花, 誠
|
| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
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. |
|
言語 |
en |
| 書誌情報 |
en : PLOS Genetics
巻 13,
号 9,
p. e1007034,
発行日 2017-09-26
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
15537390 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
15537404 |
| 出版者 |
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出版者 |
PLOS |
|
言語 |
en |
| 権利情報 |
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|
言語 |
en |
|
権利情報 |
© 2017 Kuroki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
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|
識別子 |
334032 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
pgen_13_9_e1007034.pdf (11.7 MB)
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