PLX279211

GSE76507: G9a-Mediated Methylation of ER Links the PHF20/MOF Histone Acetyltransferase Complex to Hormonal Gene Expression

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The euchromatin histone methyltransferase 2 (EHMT2, aka 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 bona fide coactivator of the endogenous estrogen receptor (ER) in breast cancer cells in a histone methylation-independent manner. G9a dimethylates ER protein at lysine 235 both in vitro and in cells. Dimethylation of ERK235 (ERK235me2) is recognized by the Tudor domain of PHF20, which in turn recruits the MOF histone acetyltransferase (HAT) complex to ER target gene promoters to deposit histone H4K16 acetylation promoting active transcription. Together, our in vitro and in vivo data establish the molecular mechanism by which G9a functions as an ER coactivator. Along with the PHF20/MOF complex, G9a links the crosstalk between ER methylation and histone acetylation governing the epigenetic regulation of hormonal gene expression. SOURCE: Yuanxin Xi (yxi@bcm.edu) - Baylor College of Medicine