CHARACTERIZATION AND DYNAMICS OF MOUSE PERICENTROMERE-ASSOCIATED DOMAINS. Mus musculus

Despite recent progress in genome topology knowledge, the role of repeats, comprising the majority of mammalian genomes, remains elusive. Satellites are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin and aggregate into nuclear chromocenters that are assumed to form a repressive compartment in the nucleus to which genes are recruited for silencing. Here we designed a strategy for genome-wide identification of pericentromere-associated domains (PADs) in different mouse cell types. The ~1000 PADs and non-PADs have similar chromatin states in embryonic stem cells. During lineage commitment however chromocenters progressively overlap with constitutively inactive genomic regions at the nuclear periphery. This suggests that chromocenters do not actively recruit PADs but are themselves attracted to inactive chromatin compartments. However, we also found that experimentally induced proximity of an active locus to chromocenters was sufficient to cause gene repression. Collectively, our data suggests that rather than being a driver of nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions to nuclear compartments where they can contribute to stably maintaining the repressed status of proximal chromosomal regions. Overall design: We performed satellite 4C (sat4C) on mouse primary thymus tissue, pluripotent mouse embryonic stem cells (ESC) and neural precursor cells (NPC) and terminally differentiated astrocytes (AC) that were sequentially derived from these ESC in vitro