Absent, small or homeotic 2 like protein (ASH2L) enhances the transcription of estrogen receptor alpha gene through GATA binding protein 3 (Gata3) [Molecular Bases of Disease]
September 25th, 2014 by Qi, J., Huo, L., Zhu, Y. T., Zhu, Y.-J.
ASH2L is a component of MLL complexes which confer H3K4 trimethylation. ASH2L gene is located at 8q11-12 which is often amplified in breast cancers. ASH2L is a component of MLL complexes which confer H3K4 trimethylation. 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 while 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 ERα gene through Gata3 to promote ERα transcription. This study established that ASH2L enhances ERα expression as a coactivator of Gata3 in breast cancers.