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Chromatin states and genomic organization impact replication timing and local patterns [ATAC-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176495 | GEO | 2021/09/27

REPOSITORIES: GEO

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Chromatin states and genomic organization impact local replication features and timing [Repli-seq]

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Chromatin states and genomic organization impact local replication features and timing [ChIP-seq]

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Two distinct modes for propagation of histone PTMs across the cell cycle

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Accurate recycling of parental histones reproduces the histone modification landscape during DNA replication

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The lysine demethylase KDM4A controls the cell-cycle expression of replicative canonical histone genes

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Epigenetic regulation of gene expression is instructed by promoter sequence and refined by developmental progression [expression]

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