Absent, Small or Homeotic 2-like Protein (ASH2L) Enhances the Transcription of the Estrogen Receptor alpha Gene through GATA-binding Protein 3 (GATA3)

作者：Qi Jin; Huo Lei; Zhu Yiwei Tony; Zhu Yi Jun^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289(45): 31373-31381.

DOI：10.1074/jbc.M114.579839

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 ER alpha expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ER alpha expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ER alpha expression in breast cancer cells. To understand the mechanism by which ASH2L regulates ER alpha 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 ER alpha gene through GATA3 to promote ER alpha transcription. This study established that ASH2L enhances ER alpha expression as a coactivator of GATA3 in breast cancers.

• 出版日期2014-11-7
• 单位西北大学