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Chromatin states and genomic organization impact local replication features and timing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175752 | GEO | 2021/09/27

REPOSITORIES: GEO

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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.

2021-09-27 | GSE175751 | GEO

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

2021-09-27 | GSE175750 | GEO

Chromatin states and genomic organization impact local replication features and timing

Project description:Chromatin states and genomic organization impact local replication features and timing

| PRJNA733482 | ENA

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.

2021-09-27 | GSE176495 | GEO

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

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

| PRJNA733485 | ENA

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

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

| PRJNA733486 | ENA

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

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

| PRJNA736434 | ENA

Combinatorial modeling of chromatin features quantitatively predicts DNA replication timing in Drosophila.

Project description:In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable for origin function, suggesting that HMs may act combinatorially in analogy to the histone code hypothesis for transcriptional regulation. In contrast to gene expression however, the relationship between combinations of chromatin features and DNA replication timing has not yet been demonstrated. Here, by exploiting a comprehensive data collection consisting of 95 CBPs and HMs we investigated their combinatorial potential for the prediction of DNA replication timing in Drosophila using quantitative statistical models. We found that while combinations of CBPs exhibit moderate predictive power for replication timing, pairwise interactions between HMs lead to accurate predictions genome-wide that can be locally further improved by CBPs. Independent feature importance and model analyses led us to derive a simplified, biologically interpretable model of the relationship between chromatin landscape and replication timing reaching 80% of the full model accuracy using six model terms. Finally, we show that pairwise combinations of HMs are able to predict differential DNA replication timing across different cell types. All in all, our work provides support to the existence of combinatorial HM patterns for DNA replication and reveal cell-type independent key elements thereof, whose experimental investigation might contribute to elucidate the regulatory mode of this fundamental cellular process.

| S-EPMC3900380 | biostudies-literature

Allele-specific control of replication timing and genome organization during development

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-26 | GSE107421 | GEO

The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells.

Project description:BackgroundThe time of locus replication during S-phase is tightly regulated and correlates with chromatin state. Embryonic stem (ES) cells have an unusual chromatin profile where many developmental regulator genes that are not yet expressed are marked by both active and repressive histone modifications. This poised or bivalent state is also characterized by locus replication in early S-phase in ES cells, while replication timing is delayed in cells with restricted developmental options.ResultsHere we used a panel of mutant mouse ES cell lines lacking important chromatin modifiers to dissect the relationship between chromatin structure and replication timing. We show that temporal control of satellite DNA replication is sensitive to loss of a variety of chromatin modifiers, including Mll, Eed, Dnmt1, Suv39h1/h2 and Dicer. The replication times of many single copy loci, including a 5 Mb contiguous region surrounding the Rex1 gene, were retained in chromatin modifier mutant ES cells, although a subset of loci were affected.ConclusionThis analysis demonstrates the importance of chromatin modifiers for maintaining correct replication of satellite sequences in pluripotent ES cells and highlights the sensitivity of some single copy loci to the influence of chromatin modifiers. Abundant histone acetylation is shown to correlate well with early replication. Surprisingly, loss of DNA methylation or histone methylation was tolerated by many loci, suggesting that these modifications may be less influential for the timing of euchromatin replication.

| S-EPMC2374999 | biostudies-literature

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