Chromatin states and genomic organization impact local replication features and timing [Repli-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE175751 | GEO | 2021/09/27
REPOSITORIES: GEO
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Project description:Replication timing (RT) associates with genome architecture, while having a mixed relationship to histone marks. By profiling replication at high-resolution and systematically assessing broad and focused histone marks across cell cycle with and without genetic perturbation, we address the causal relationship between histone marks, their associated states and RT. Our approach identified four chromatin states, including a previously uncharacterized H3K36me2 state, that defined 97% of the mappable genome. RT and local replication patterns (e.g., initiation zones) quantitatively associate with chromatin states, histone mark dynamics, and spatial chromatin structure. Furthermore, overexpression of the histone H3 lysine 9/36 tri-demethylase KDM4A impacts RT genome-wide (11%), which is linked to KDM4A-associated histone marks and clusters of enhancer elements. Lastly, replication within H3K36me2-enriched neighborhoods is sensitive to KDM4A overexpression and is controlled at a megabase-scale. These studies establish a critical role for chromatin regulation in regulating RT and the local RT patterns.
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