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Histone H3K9 methyltransferase G9a represses PPAR γ expression and adipogenesis
Author(s) -
Wang Lifeng,
Xu Shiliyang,
Lee JiEun,
Baldridge Anne,
Grullon Sean,
Peng Weiqun,
Ge Kai
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.306
Subject(s) - biology , methyltransferase , adipogenesis , histone methyltransferase , ezh2 , histone , histone h3 , microbiology and biotechnology , methylation , genetics , gene , mesenchymal stem cell
PPARγ promotes adipogenesis while Wnt proteins inhibit adipogenesis. However, the mechanisms that control expression of these positive and negative master regulators of adipogenesis remain incompletely understood. By genome‐wide histone methylation profiling in preadipocytes, we find that among gene loci encoding adipogenesis regulators, histone methyltransferase (HMT) G9a‐mediated repressive epigenetic mark H3K9me2 is selectively enriched on the entire PPAR γ locus. H3K9me2 and G9a levels decrease during adipogenesis, which correlates inversely with induction of PPAR γ. Removal of H3K9me2 by G9a deletion enhances chromatin opening and binding of the early adipogenic transcription factor C/EBPβ to PPAR γ promoter, which promotes PPAR γ expression. Interestingly, G9a represses PPAR γ expression in an HMT activity‐dependent manner but facilitates Wnt10a expression independent of its enzymatic activity. Consistently, deletion of G9a or inhibiting G9a HMT activity promotes adipogenesis. Finally, deletion of G9a in mouse adipose tissues increases adipogenic gene expression and tissue weight. Thus, by inhibiting PPAR γ expression and facilitating Wnt10a expression, G9a represses adipogenesis.