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

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

PROVIDER: PRJNA736434 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14768461_1.fastq.gz	Fastqsanger.gz
	SRR14768461_2.fastq.gz	Fastqsanger.gz
	SRR14768462_1.fastq.gz	Fastqsanger.gz
	SRR14768462_2.fastq.gz	Fastqsanger.gz
	SRR14768463_1.fastq.gz	Fastqsanger.gz

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Chromatin states and genomic organization impact local replication features and timing

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

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

Project description:Replication timing (RT) control is linked to histone modifications (HMs) and genome architecture. However, HM landscape across cell cycle and its relationship with RT and chromatin modifiers have not been comprehensively assessed. Here we perform detailed replication profiling together with cell cycle profiling of multiple HMs, ATAC-seq, and gene expression. We classify 97% of the genome into four gross chromatin states, including a previously uncharacterized intergenic H3K36me2 state. RT and associated replication features (e.g. initiation zones) quantitatively associate with these chromatin states, HM dynamics, and spatial chromatin structure. Furthermore, overexpression of the histone H3 lysine 9/36 tri-demethylase KDM4A impacts RT across 12% of the genome. RT regulation is strongly linked to KDM4A-associated HMs and enhancer-like elements. Lastly, replication within the intergenic H3K36me2 neighborhoods is sensitive to KDM4A overexpression and is controlled as wide megabase-scale units. In conclusion, these studies establish a critical role for chromatin regulation in directing RT genome-wide.

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