G9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression

• Published in: Nature communications 2016-03, Vol.7 (1), p.10810-12, Article 10810
• Main Authors: Zhang, Xi, Peng, Danni, Xi, Yuanxin, Yuan, Chao, Sagum, Cari A., Klein, Brianna J., Tanaka, Kaori, Wen, Hong, Kutateladze, Tatiana G., Li, Wei, Bedford, Mark T., Shi, Xiaobing
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/109; 38; 38/15; 38/39; 38/43; 38/77; 631/337/458/1648; 631/67/1059/602; 631/67/1347; 631/80/86; 82; Acetylation; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast Neoplasms - genetics; Cell Line, Tumor; Epigenesis, Genetic; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; HEK293 Cells; Histocompatibility Antigens - genetics; Histocompatibility Antigens - metabolism; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Humanities and Social Sciences; Humans; Immunoprecipitation; In Vitro Techniques; Magnetic Resonance Spectroscopy; MCF-7 Cells; multidisciplinary; Nuclear Receptor Coactivator 2; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10810

The euchromatin histone methyltransferase 2 (also known as G9a) methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors. The molecular mechanisms underlying this activation remain elusive. Here we show that G9a functions as a coactivator of the endogenous oestrogen receptor α (ERα) in breast cancer cells in a histone methylation-independent manner. G9a dimethylates ERα at K235 both in vitro and in cells. Dimethylation of ERαK235 is recognized by the Tudor domain of PHF20, which recruits the MOF histone acetyltransferase (HAT) complex to ERα target gene promoters to deposit histone H4K16 acetylation promoting active transcription. Together, our data suggest the molecular mechanism by which G9a functions as an ERα coactivator. Along with the PHF20/MOF complex, G9a links the crosstalk between ERα methylation and histone acetylation that governs the epigenetic regulation of hormonal gene expression. The histone methyltransferase G9a methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors. Here, Zhang et al . show that methylation of ERα by G9a recruits the PHF20/MOF complex that deposits histone H4K16 acetylation promoting active transcription.