Lopez-Garcia Jorge, Periyasamy Manikandan, Thomas Ross S, Christian Mark, Leao Maria, Jat Parmjit, Kindle Karin B, Heery David M, Parker Malcolm G, Buluwela Lakjaya, Kamalati Tahereh, Ali Simak
Department of Oncology, Imperial College London, Du Cane Road, London W12 0NN, UK.
Nucleic Acids Res. 2006;34(21):6126-36. doi: 10.1093/nar/gkl875. Epub 2006 Nov 3.
The regulation of gene expression by estrogen receptor-alpha (ERalpha) requires the coordinated and temporal recruitment of diverse sets of transcriptional co-regulator complexes, which mediate nucleosome remodelling and histone modification. Using ERalpha as bait in a yeast two-hybrid screen, we have identified a novel ERalpha-interacting protein, ZNF366, which is a potent corepressor of ERalpha activity. The interaction between ZNF366 and ERalpha has been confirmed in vitro and in vivo, and is mediated by the zinc finger domains of the two proteins. Further, we show that ZNF366 acts as a corepressor by interacting with other known ERalpha corepressors, namely RIP140 and CtBP, to inhibit expression of estrogen-responsive genes in vivo. Together, our results indicate that ZNF366 may play an important role in regulating the expression of genes in response to estrogen.
雌激素受体α（ERα）对基因表达的调控需要多种转录共调节复合物的协同和适时募集，这些复合物介导核小体重塑和组蛋白修饰。我们在酵母双杂交筛选中以ERα作为诱饵，鉴定出一种新型的与ERα相互作用的蛋白ZNF366，它是ERα活性的强效共抑制因子。ZNF366与ERα之间的相互作用已在体外和体内得到证实，且由这两种蛋白的锌指结构域介导。此外，我们发现ZNF366通过与其他已知的ERα共抑制因子RIP140和CtBP相互作用，在体内抑制雌激素反应性基因的表达，从而发挥共抑制因子的作用。总之，我们的结果表明ZNF366可能在雌激素响应基因的表达调控中发挥重要作用。
