title: Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor α gene through GATA-binding protein 3 (GATA3).
abstract: ASH2L is a component of MLL complexes that confer H3K4 trimethylation. The ASH2L gene is located at 8q11-12, which is often amplified in breast cancers. We found that increased ASH2L expression, which can result from gene amplification, is often correlated with increased ERα expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ERα expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ERα expression in breast cancer cells. To understand the mechanism by which ASH2L regulates ERα expression, we identified GATA3 as the binding protein of ASH2L. ASH2L was shown to potentiate the transcriptional activity of GATA3. ASH2L was recruited to the enhancer of the ERα gene through GATA3 to promote ERα transcription. This study established that ASH2L enhances ERα expression as a coactivator of GATA3 in breast cancers.
authors.affiliation: From the Maternal and Child Hospital of Shaanxi Province, Xian, Shaanxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: the Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, and.
authors.forename: Lei
authors.initials: L
authors.lastname: Huo
authors.affiliation: the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Yiwei Tony
authors.initials: YT
authors.lastname: Zhu
authors.affiliation: the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611 y-zhu2@northwestern.edu.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: C485622:ASH2L protein, human; C120115:Ash2l protein, mouse; D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D050990:GATA3 Transcription Factor; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: Breast Cancer; Estrogen Receptor; GATA Transcription Factor; Gene Regulation; Oncogene