title: Characterization and dynamics of pericentromere-associated domains in mice.
abstract: Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellite 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. We have 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 suggest 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.
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Wijchers
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Geeven
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Eyres
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Atze J
authors.initials: AJ
authors.lastname: Bergsma
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Janssen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Marjon
authors.initials: M
authors.lastname: Verstegen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Yori
authors.initials: Y
authors.lastname: Schell
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vermeulen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics*; D022041:Euchromatin; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods; D006570:Heterochromatin; D051379:Mice; D018598:Minisatellite Repeats; D015533:Transcriptional Activation
chemical_list: D022041:Euchromatin; D006570:Heterochromatin