Histone methylation by the methyltransferase G9a causes gene silencing, whereas the interaction of G9a with nuclear receptors such as oestrogen receptor-α (ERα) leads to gene activation through a poorly understood mechanism. Zhang et al. showed that the depletion of G9a in ER-expressing breast cancer cell lines reduced oestrogen-induced activation of hundreds of genes, as well as cell proliferation and transformation. These effects were at least partially dependent on the methyltransferase activity of G9a that dimethylated ERα at Lys235, leading to the binding of ERα by PHF20, which is a subunit of the histone acetyltransferase complex MOF. Following oestrogen treatment, G9a-dependent interaction of MOF with ERα at ERα target gene promoters induced histone H4 Lys16 acetylation and enhanced transcription.
References
Zhang, X. et al. G9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression. Nat. Commun. 7, 10810 (2016)
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Zlotorynski, E. ERα activation through methylation. Nat Rev Mol Cell Biol 17, 265 (2016). https://doi.org/10.1038/nrm.2016.54
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DOI: https://doi.org/10.1038/nrm.2016.54