In order to distinguish between these models, it will be important to explore cases of Dabrafenib cell line null domain insulation, especially when not involving actively transcribed units. It will also be

critical to assess the repressive nature of null domains, and to ask if this chromosomal configuration participate in securing gene silencing, or is a mere consequence of it. Hp1 and Polycomb domains. In flies, a second type of repressive chromatin domains contain heterochromatin components HP1 and Su(var)3–9, as well as the cognate H3K9 methylation marks [ 11 and 22••]. This type of chromatin is most prominent in regions surrounding centromeres and in subtelomeric regions, and it is likely that mammalian chromosomes also include such domains, although they are more difficult to map owing to their high repetitive content. Intrestingly, Hi-C maps show a clear tendency for heterochromatic regions located in different chromosomes to cluster via interchromosomal contacts. By contrast, Polycomb domains, which form a third type of repressive chromatin DAPT in Drosophila, are characterized by a different

contact behavior. Polycomb domains are excluded from pericentromeric regions and contain hundreds of genes in the euchromatic arms of chromosomes. Despite the fact that some of the chromatin components of Polycomb domains are shared with HP1 chromatin [ 22••], the presence of Polycomb proteins changes the contact behavior of these regions. Globally, Polycomb proteins form nuclear compartments called Polycomb bodies [ 34, 35, 36 and 37] and Hi-C confirm the idea that Polycomb domains establish a network of contacts at these nuclear bodies [ 38 and 39]. In contrast to Hp1 domains, Polycomb domains in flies preferentially contact other Polycomb domains in the

same chromosome arm [ 8•• and 39], although cases of Polycomb-mediated interchromosomal contacts have been reported in transgenic fly lines [ 35 and 40]. In some cases, such as for Hox genes, these contacts stabilize Polycomb dependent silencing [ 38]. Whether this is a general phenomenon, however, is still not known. It will be interesting to investigate whether Polycomb-mediated contacts in vertebrates are also mostly occurring among loci located in the ALOX15 same chromosome and to what extent the physical genomic expansion promoted detachment of Polycomb domain clusters within and between chromosomes. Genomic compartmentalization. The emergence of 4C profiles and Hi-C maps brought 3C to the forefront of epigenetic research, and the discovery of topological domains is beginning to provide building blocks for the systematic construction of physical models for genome function. Large metazoan genomes are now understood to be organized into objects that can serve as genomic compartments.