The Non-classical Mechanisms By Which Estrogen Receptors Regulate Target Genes Transcription

The steroid hormone 17β-estradiol (E2) is a key regulator. The mechanisms of its transcriptional regulation are very complicated. The classical mechanism of E2 involves estrogen binding to receptors in the nucleus, after which the receptors dimerize and bind to specific response elements known as estrogen response elements (EREs) located in the promoters of target genes. However, ERs can also regulate gene expression through protein-protein interactions with other DNA-binding transcription factors in the nucleus, or through regulation with production and activity of other genes. It is very important to study non-classical 17β-estradiol effects to reveal mechanisms of estrogen function. And provide some new ways to design new antagonist and agonist of ER. In this study we used JEG-3 cell lines and MG-63 cell lines as model systems to exam non-classical effects of different domains of ER on E2 and SERMs induced transcriptional regulation. Our results showed that 1. DNA binding domain was dependent to the transcription repression of E2, and ligand bingding domain especially AF-2 was the key domain for the transcription repression. The integrity of zinc-figure in DBD andα-helix in AF-2 were very important. However, sites which had roles may be different in specific type cells. 2. It was different that transcriptional regulation of CRE gene by SERMs in different type cells. The integrity of zinc-figure in DBD was dependent to the transcriptional regulation of SERMs. AF-2 was also a key role, but specific sites worked in specific type cells. 3. PKC can regulate transcription of ERE through ERβ. It showed differently in different type cells.