Regulation of Estrogen Receptor α by the SET7 Lysine Methyltransferase

Krithika Subramanian, Da Jia, Priya Kapoor-Vazirani, Doris R. Powell, Robert E. Collins, Dipali Sharma, Junmin Peng, Xiaodong Cheng, Paula M. Vertino

Research output: Contribution to journalArticlepeer-review

197 Scopus citations


Estrogen receptor α (ER) is a ligand-dependent transcription factor. Upon binding estrogen, ER recruits coactivator complexes with histone acetyltransferase or methyltransferase activities to activate downstream target genes. In addition to histones, coactivators can modify ER itself and other proteins in the transactivation complex. Here, we show that ER is directly methylated at lysine 302 (K302) by the SET7 methyltransferase. SET7-mediated methylation stabilizes ER and is necessary for the efficient recruitment of ER to its target genes and for their transactivation. The SET7-ER complex structure reveals the molecular basis for ER peptide recognition and predicts that modifications or mutations of nearby residues would affect K302 methylation. Indeed, a breast cancer-associated mutation at K303 (K303R) alters methylation at K302 in vitro and in vivo. These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generate "ER modification cassettes" that yield distinct patterns for signaling downstream events.

Original languageEnglish (US)
Pages (from-to)336-347
Number of pages12
JournalMolecular cell
Issue number3
StatePublished - May 9 2008
Externally publishedYes


  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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