Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer [ChIP-seq]

ABSTRACT: DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-Seq and integrated epigenome analyses and demonstrate that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing. A subset of altered replication timing domains are conserved across cancers from different tissue origins. Notably, late-replicating regions in cancer cells display a loss of DNA methylation, and a switch in heterochromatin features from H3K9me3-marked constitutive to H3K27me3-marked facultative heterochromatin. Finally, analysis of 214 prostate and 35 breast cancer genomes reveal that late-replicating regions are prone to cis and early-replication to trans chromosomal rearrangements. Together, our data suggests that the nature of chromosomal rearrangement in cancer is related to the spatial and temporal positioning and altered epigenetic states of early-replicating compared to late-replicating loci.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98714 | GEO | 2019/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer [Repli-seq]

Project description:DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-Seq and integrated epigenome analyses and demonstrate that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing. A subset of altered replication timing domains are conserved across cancers from different tissue origins. Notably, late-replicating regions in cancer cells display a loss of DNA methylation, and a switch in heterochromatin features from H3K9me3-marked constitutive to H3K27me3-marked facultative heterochromatin. Finally, analysis of 214 prostate and 35 breast cancer genomes reveal that late-replicating regions are prone to cis and early-replication to trans chromosomal rearrangements. Together, our data suggests that the nature of chromosomal rearrangement in cancer is related to the spatial and temporal positioning and altered epigenetic states of early-replicating compared to late-replicating loci.

2019-01-23 | GSE98730 | GEO

Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer [Bisulfite-Seq]

2019-01-23 | GSE124274 | GEO

Heterochromatin protein 1 (HP1) modulates replication timing of Drosophila heterochromatin

Project description:The replication of a genomic region during S-phase can be highly dynamic between cell types that differ in transcriptome and epigenome. Replication timing has been positively correlated with several histone modifications that occur at active genes, while repressive histone modifications mark late replicating regions. This raises the question if chromatin modulates the initiating events of replication. To gain insights into this question we have studied the function of heterochromatin protein 1 (HP1), a reader of to the repressive histone lysine 9 methylation of H3, in genome-wide organization of replication. Cells with reduced levels of HP1 show an advanced replication timing of centromeric repeats in agreement with the model that repressive chromatin mediates the very late replication of large clusters of constitutive heterochromatin. Surprisingly however regions with high levels of interspersed repeats on the chromosomal arms in particular on chromosome 4 and in pericentromeric regions of chromosome 2 behave differently. Here loss of HP1 results in delayed replication timing. The fact that these regions are bound by HP1 suggests a direct effect. Thus while HP1 mediates very late replication of centromeric DNA it is also required for early replication of autosomal regions with high levels of repeats. This observation of opposing functions of HP1 suggests a model where repeat inactivation on autosomes is required for proper activation of origins of replication that fire early, while HP1 mediated repression at constitutive heterochromatin is required to ensure replication of centromeric repeats at the end of S phase. Keywords: RNAi, chip-chip, replication timing

2010-03-16 | GSE18092 | GEO

The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [BrdU-IP]

Project description:Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the context of development and disease. DNA methylation by DNA methyltransferases (DNMTs) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell biological and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various DNMT-mutant mouse ES cell lines that include a line with a drug-inducible DNMT3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) correlates with redistribution of H3K27me3 induced upon DNA hypomethylation: later replicating PH coincides with H3K27me3 enriched regions. In contrast, this relationship with H3K27me3 was not evident at chromosomal arm regions that undergo either early-to-late (EtoL) or late-to-early (LtoE) replication timing switching upon loss of DNMTs. Interestingly, transcriptional up- and down-regulation frequently coincide with earlier and later shifts in replication timing of chromosomal arm regions, respectively. Our study revealed previously unrecognized complex and diverse roles of DNMTs in shaping the mammalian DNA replication landscape.

2021-02-12 | GSE119405 | GEO

Trophoblast giant cell underrepresentation (tiling)

Project description:We profiled trophoblast stem cell replication-timing in order to compare these data to our data on underrepresented (UR) domainss in trophoblast giant cells (polyploid cells derived from 2N trophoblast stem cells). We found that UR domains are formed from late-replicating regions in tropoblast stem cells. Profile of early and late replicating regions in cultured trophoblast stem cells.

2014-05-29 | E-GEOD-50207 | biostudies-arrayexpress

The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [microarray]

2021-02-12 | GSE119406 | GEO

DNA methylation maintains integrity of higher order genome architecture (Nanopore)

Project description:DNA replication timing and 3D chromatin organisation are associated with epigenomic changes across large domains during human differentiation and cancer progression. However, it is unclear if epigenome changes, in particular cancer-associated DNA hypomethylation, is a consequence or cause of changes observed in higher order genome architecture. Here, we compare replication timing profiles and three dimensional (3D) genome organisation, using Hi-C and single cell Repli-Seq in the DNMT1 and DNMT3B DNA methyltransferases double knockout hypomethylated DKO1 colorectal cancer cell line and its parental HCT116 cell line. We find that the hypomethylated cells show a profound loss of replication timing precision, gain of single cell replication timing heterogeneity and loss of chromatin conformation integrity. Discrete regions, that undergo a large change in replication timing in the hypomethylated cells, are associated with a loss of allelic replication timing and shrinking of late replicating Partially Methylated Domain (PMD) boundaries. In contrast, conservation of replication timing after DNA methylation depletion at PMDs is associated with the formation of new H3K9me3/H3K4me3 bivalent domains which may serve to prevent ectopic transcription and maintain cell viability. Together our results show that a loss of global methylation, a common hallmark of cancer, directly impacts on the precision of replication timing and contribute to deregulation of the 3D chromatin architecture.

2021-09-21 | GSE159663 | GEO

DNA methylation maintains integrity of higher order genome architecture (RNA-Seq)

2021-09-21 | GSE159664 | GEO

DNA methylation maintains integrity of higher order genome architecture (WGBS)

2021-09-21 | GSE158010 | GEO

DNA methylation maintains integrity of higher order genome architecture (single cell Repli-Seq)

2021-09-21 | GSE158009 | GEO