Regulation of Egr1 Target Genes by the NuRD Chromatin Remodeling Complex

摘要

Previous work had shown that the EGR1 transactivator is overexpressed in prostate cancer, while expression of its corepressor, NAB2, is reduced. Based on our recent characterization of an interaction between NAB2 and the NuRD (Nucleosome remodeling and disruption) chromatin remodeling complex, we have determined if loss of NAB2 expression results in loss of NuRD targeting to EGR1 target genes. In progress thus far, we have shown that repression of some NAB-regulated target genes in prostate cancer cells requires the NuRD chromatin remodeling complex. We have developed novel chromatin immunoprecipitation assays for the NuRD complex in prostate cells to demonstrate the colocalization of the NuRD complex on EGR1-regulated endogenous target genes. In addition, we have shown that recruitment of the NuRD complex to EGR1 target genes is dependent on NAB2. Finally, NuRD-dependent repression of NAB-regulated repression is sensitive to histone deacetylase inhibitors. These results provide the first functional description of one of the major HDAC- containing chromatin remodeling complexes in prostate cancer cells, and elucidate molecular consequences of loss of NAB2 corepressor function in prostate carcinogenesis by analyzing the mechanism of NAB2 corepressor function.