Regulation of genic transactivation and transrepression mediated by nuclear receptors

Abstract

The mechanisms in which the organisms coordinate the hormone signaling with environmental effects, though not perfectly understood, have been elucidated by studies of transcription factors (TF), like nuclear receptors (RNs). The regulation of these proteins exists to promote a common control of gene expression in different tissues and developmental stages. The RNs are closely related to diseases like cancer, metabolic syndrome, diabetes, cardiophaties and obesity. They can act directly or indirectly in the regulation of transcription. In the direct regulation, RNs activate or represses the gene expression though their ligand modulation (transactivation). The indirect process occurs when RNs acts under other transcription factors (transrepression). Many studies have shown the direct participation of RNs in the transcription activation and repression. Others reported the influence of interaction of TFs and some nuclear receptors in diverse proteins expression regulation processes. In this context, the importance of a better understanding about the interaction among RNs and other proteins, besides the mechanisms of transactivation and transrepression, is evident. Furthermore, this project purposes the study of interactions between RNs and DNA regulatory sequences (HREs); RNs and coregulators proteins; and RNs and transcription factors. These studies will be made by biochemical, biophysical and structural biology point of views, through the following experiments: pull down, imunoprecipitation, real time PCR, cell culture transactivation, affinity assays, fluorescence, circular dichroism, small angle X-ray scattering, light scattering and protein crystallography. The results will be used in order to seek more information about their action mechanisms, allowing that new regulation models of transcriptional regulation mediated by NRs could be purposed. Or even, that the already purposed models could be confirmed in a higher degree of details. (AU)