Characterization and dynamics of pericentromere-associated domains in mice

Patrick J Wijchers, Geert Geeven, Michael Eyres, Atze J Bergsma, Mark Janssen, Marjon Verstegen, Yun Zhu, Yori Schell, Carlo Vermeulen, Elzo de Wit, Wouter de Laat

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellites repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin and aggregate into nuclear chromocenters. These nuclear landmark structures 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, but during lineage commitment chromocenters progressively associate with constitutively inactive genomic regions at the nuclear periphery. This suggests that PADs are not actively recruited to chromocenters, but that chromocenters 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 driving nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions into nuclear compartments where they can contribute to stable maintenance of the repressed status of proximal chromosomal regions.

Original languageEnglish
JournalGenome Research
DOIs
Publication statusPublished - 16 Apr 2015

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