PMID- 25258321 OWN - NLM STAT- MEDLINE DCOM- 20150117 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 45 DP - 2014 Nov 7 TI - Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor alpha gene through GATA-binding protein 3 (GATA3). PG - 31373-81 LID - 10.1074/jbc.M114.579839 [doi] AB - 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 ERalpha expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ERalpha expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ERalpha expression in breast cancer cells. To understand the mechanism by which ASH2L regulates ERalpha 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 ERalpha gene through GATA3 to promote ERalpha transcription. This study established that ASH2L enhances ERalpha expression as a coactivator of GATA3 in breast cancers. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Qi, Jin AU - Qi J AD - From the Maternal and Child Hospital of Shaanxi Province, Xian, Shaanxi, China. FAU - Huo, Lei AU - Huo L AD - the Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, and. FAU - Zhu, Yiwei Tony AU - Zhu YT AD - the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611. FAU - Zhu, Yi-Jun AU - Zhu YJ AD - the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611 y-zhu2@northwestern.edu. LA - eng GR - R01 CA088898/CA/NCI NIH HHS/United States GR - CA 88898/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140925 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (ASH2L protein, human) RN - 0 (Ash2l protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (GATA3 Transcription Factor) RN - 0 (Histones) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Binding Sites MH - Breast Neoplasms/metabolism MH - Cell Line MH - Cell Line, Tumor MH - DNA-Binding Proteins/genetics/*physiology MH - Enhancer Elements, Genetic MH - Estrogen Receptor alpha/genetics/*metabolism MH - Female MH - GATA3 Transcription Factor/*metabolism MH - Gene Expression Regulation MH - *Gene Expression Regulation, Neoplastic MH - HEK293 Cells MH - Histones/metabolism MH - Humans MH - Mice MH - Nuclear Proteins/genetics/*physiology MH - Signal Transduction MH - Transcription Factors/genetics/*physiology MH - Transcription, Genetic MH - Two-Hybrid System Techniques PMC - PMC4223337 OTO - NOTNLM OT - Breast Cancer OT - Estrogen Receptor OT - GATA Transcription Factor OT - Gene Regulation OT - Oncogene EDAT- 2014/09/27 06:00 MHDA- 2015/01/18 06:00 PMCR- 2015/11/07 CRDT- 2014/09/27 06:00 PHST- 2014/09/27 06:00 [entrez] PHST- 2014/09/27 06:00 [pubmed] PHST- 2015/01/18 06:00 [medline] PHST- 2015/11/07 00:00 [pmc-release] AID - S0021-9258(20)33364-0 [pii] AID - M114.579839 [pii] AID - 10.1074/jbc.M114.579839 [doi] PST - ppublish SO - J Biol Chem. 2014 Nov 7;289(45):31373-81. doi: 10.1074/jbc.M114.579839. Epub 2014 Sep 25.