C1: Epigenetic function of the “Nucleosome Remodelling and Histone Deacetylase” (NuRD) complex

There are several indications that not only methylated DNA causes heterochromatic chromatin modification, but also that a specific chromatin modification may induce DNA methylation. Therefore, the causal relationship between DNA methylation, histone deacetylation, histone methylation and gene repression will be analyzed. Previously, we have identified isolator sites next to important tumor relevant genes. These very likely function in restricting possible heterochromatic modifications to regions outside of e.g. tumor suppressor genes. The repressive status of chromatin is often mediated by the “Nucleosome Remodeling and Histone Deacetylase” (NuRD) complex. The goal of this project is to identify the mechanisms by which NuRD and other heterochromatic components override isolators in case of the pathological inactivation of tumor suppressor genes