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G9A covers all bases

Nature Reviews Molecular Cell Biology volume 14, page 5 (2013)Cite this article

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G9A is primarily responsible for histone H3 dimethylation at Lys9 (H3K9me2), which is thought to promote gene silencing. The authors observed that H3K9me2 levels were high specifically on the Pparg locus but were low on genes encoding other regulators of adipogenesis. Moreover, H3K9me2 levels on Pparg markedly decreased during adipocyte differentiation. Consistent with this, G9A was enriched throughout the promoter and gene body regions of both PPARγ isoforms (Pparg1 and Pparg2). Moreover, G9A deletion significantly increased Pparg2 expression by promoting the binding of the transcription factor C/EBPβ (CCAAT/enhancer-binding protein-β) to the Pparg2 promoter, ultimately enhancing adipogenesis. Together, these findings suggest that G9A inhibits adipogenesis by adding a repressive H3K9me2 mark on the Pparg promoter.

Interestingly, the authors observed that depletion of G9A also decreased the expression of WNT10A and attenuated canonical WNT signalling, which is thought to inhibit adipogenesis. This effect could be rescued through the addition of G9A or of G9A lacking enzymatic activity. Similarly, administration of the G9A inhibitor BIX01294 — which specifically interferes with the methyltransferase activity and decreases H3K9me2 levels — increased Pparg expression but had no effect on WNT10A expression. Thus, G9A seems to promote WNT10A expression independently of its enzymatic activity.

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References

ORIGINAL RESEARCH PAPER

  1. Wang, L. et al. Histone H3K9 methyltransferase G9a represses PPARγ expression and adipogenesis. EMBO J. 23 Nov 2012 (doi:10.1038/emboj.2012.306)

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FURTHER READING

  1. Cristancho, A. G. & Lazar, M. A. Forming functional fat: a growing understanding of adipocyte differentiation. Nature Rev. Mol. Cell Biol. 12, 722–734 (2011)

    Article  CAS  Google Scholar 

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Authors
  1. Rachel David
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David, R. G9A covers all bases. Nat Rev Mol Cell Biol 14, 5 (2013). https://doi.org/10.1038/nrm3497

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