Document Detail


Functional dynamics of H3K9 methylation during meiotic prophase progression.
MedLine Citation:
PMID:  17599069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. G9a is a major mammalian H3K9 methyltransferase at euchromatin and is essential for mouse embryogenesis. Here we describe the roles of G9a in germ cell development. Mutant mice in which G9a is specifically inactivated in the germ-lineage displayed sterility due to a drastic loss of mature gametes. G9a-deficient germ cells exhibited perturbation of synchronous synapsis in meiotic prophase. Importantly, mono- and di-methylation of H3K9 (H3K9me1 and 2) in G9a-deficient germ cells were significantly reduced and G9a-regulated genes were overexpressed during meiosis, suggesting that G9a-mediated epigenetic gene silencing is crucial for proper meiotic prophase progression. Finally, we show that H3K9me1 and 2 are dynamically and sex-differentially regulated during the meiotic prophase. This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis.
Authors:
Makoto Tachibana; Masami Nozaki; Naoki Takeda; Yoichi Shinkai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-28
Journal Detail:
Title:  The EMBO journal     Volume:  26     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-26     Completed Date:  2007-09-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  3346-59     Citation Subset:  IM    
Affiliation:
Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan. mtachiba@virus.kyoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Lineage
Female
Gene Deletion
Gene Expression Regulation
Histone-Lysine N-Methyltransferase / deficiency,  metabolism
Histones / metabolism*
Infertility / enzymology
Integrases / metabolism
Jumonji Domain-Containing Histone Demethylases
Kinetics
Lysine / metabolism*
Male
Meiotic Prophase I*
Methylation
Mice
Mice, Knockout
Ovary / abnormalities,  enzymology,  pathology
Oxidoreductases, N-Demethylating / metabolism
Pachytene Stage
Protein Methyltransferases
Spermatocytes / cytology,  enzymology
Spermatogonia / cytology,  enzymology
Chemical
Reg. No./Substance:
0/Histones; 56-87-1/Lysine; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases; EC 1.14.11.-/Kdm3a protein, mouse; EC 1.5.-/Oxidoreductases, N-Demethylating; EC 2.1.1.-/Protein Methyltransferases; EC 2.1.1.-/histone methyltransferase; EC 2.1.1.43/Histone-Lysine N-Methyltransferase; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections

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