number of access : ?
number of downloads : ?
ID 114323
Title Alternative
Tuning of Sry expression by H3K9 methylation and demethylation
Author
Baba, Shoko Kyoto University
Maeda, Ryo Tokushima University
Miyawaki, Shingo Tokushima University
Yamaguchi, Miyoko Tokushima University
Kitano, Satsuki Kyoto University
Miyachi, Hitoshi Kyoto University
Itoh, Akihiro RIKEN Center for Sustainable Resource Science
Yoshida, Minoru RIKEN Center for Sustainable Resource Science
Content Type
Journal Article
Description
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.
Journal Title
PLOS Genetics
ISSN
15537390
15537404
Publisher
PLOS
Volume
13
Issue
9
Start Page
e1007034
Published Date
2017-09-26
Rights
© 2017 Kuroki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences
Technical Support Department