Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain
Ontology highlight
ABSTRACT:
ORGANISM(S): Gallus gallus
PROVIDER: GSE153566 | GEO | 2020/09/07
REPOSITORIES: GEO
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Project description:Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into A/B compartments. Until now, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late-replicating region for earlier replication. The two origins overlap with a constitutive or a silent tissue-specific promoter. When inserted side-by-side, these modules advance replication timing over a 250 kb region through the cooperation with one endogenous origin located 30 kb away. Moreover, when inserted at two chromosomal sites separated by 30 kb, these two modules come into close physical proximity and form an early-replicating domain establishing more contacts with active A compartments. The synergy depends on the presence of the active promoter/origin. Our results show that clustering of strong origins located at active promoters can establish early-replicating domains.
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Project description:Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain
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Project description:Polycomb group (PcG) proteins mediate heritable but reversible silencing of developmental regulator genes by modifying their chromatin configuration. Accumulating evidence documents a role for PcG proteins in regulating higher order chromatin structures likely by their clustering, however, underlying mechanisms and its impact on transcriptional regulation remain obscure. In this study, we found that subnuclear clustering of PRC1 at canonical PcG target genes depended on head-to-tail polymerization property of SAM domain of Phc2 and likely Phc1. We show that Phc2-SAM polymerization limits the dynamic nature of PRC1, thereby promotes stable association of PRC1 with PcG target genes and contributes to their robust silencing. Our findings suggest a novel model by which SAM polymerization of Phc2 modulates the structural organization of PcG complexes to enable robust yet reversible PcG-mediated repression during development.
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