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The nuclear hormone receptor estrogen receptora (ERa) promotes cellular growth through ligand- dependent activation of specific target genes, a process which is targeted in the treatment of ERa- expressing breast cancers. ERa activity is regulated at the protein level by post-translational modifications including phosphorylation and acetylation. A study now shows that ERa can also be directly methylated at lysine 302 (K302) by SET7, a histone methyltransferase that is known to monomethylate H3K4 and is associated with transcriptional activation. It was shown that K302 methylation stabilizes ERa protein and is suggested to increase sensitivity of ERa to estrogens, enhancing transcription of estrogen response elements. Furthermore, SET7 methylation of K302 is enhanced by a breast cancer-associated mutation at K303 (K303R) in vitro. These findings provide an additional mechanism of SET7 mediated transcriptional activation, as well as potential insight into the complex regulation of ERa stability and ligand sensitivity. Endocrine-Related Cancer (2009) 16 319-323

Epigenetics meets estrogen receptor: regulation of estrogen receptor by direct lysine methylation