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 journalArticle

Abstract

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
Volume30
Issue number3
DOIs
StatePublished - May 9 2008

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Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Subramanian, K., Jia, D., Kapoor-Vazirani, P., Powell, D. R., Collins, R. E., Sharma, D., Peng, J., Cheng, X., & Vertino, P. M. (2008). Regulation of Estrogen Receptor α by the SET7 Lysine Methyltransferase. Molecular cell, 30(3), 336-347. https://doi.org/10.1016/j.molcel.2008.03.022