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

Xi Zhang; Danni Peng; Yuanxin Xi; Chao Yuan; Cari A Sagum; Brianna J Klein; Kaori Tanaka; Hong Wen; Tatiana G Kutateladze; Wei Li; Mark T Bedford; Xiaobing Shi

doi:10.1038/ncomms10810

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

Nat Commun. 2016 Mar 10:7:10810. doi: 10.1038/ncomms10810.

Authors

Xi Zhang^{1

2}, Danni Peng^{1

2}, Yuanxin Xi³, Chao Yuan^{1

2}, Cari A Sagum^{1

2}, Brianna J Klein⁴, Kaori Tanaka^{1

2}, Hong Wen^{1

2}, Tatiana G Kutateladze⁴, Wei Li³, Mark T Bedford^{1

2

5}, Xiaobing Shi^{1

2

5}

Affiliations

¹ Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
² Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
³ Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
⁴ Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
⁵ The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030, USA.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / metabolism
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Breast Neoplasms / genetics*
Cell Line, Tumor
DNA-Binding Proteins
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
Humans
Immunoprecipitation
In Vitro Techniques
MCF-7 Cells
Magnetic Resonance Spectroscopy
Nuclear Receptor Coactivator 2
Promoter Regions, Genetic
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors

Substances

Antigens, Neoplasm
Biomarkers, Tumor
DNA-Binding Proteins
ESR1 protein, human
Estrogen Receptor alpha
Histocompatibility Antigens
NCOA2 protein, human
Nuclear Receptor Coactivator 2
PHF20 protein, human
Transcription Factors
EHMT2 protein, human
Histone-Lysine N-Methyltransferase
Histone Acetyltransferases
KAT8 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding