Human DNA Replication Timing Variation
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ABSTRACT:
PROVIDER: PRJNA598744 | ENA |
REPOSITORIES: ENA
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Project description:Human DNA Replication Timing Variation
| PRJNA598743 | ENA
Project description:DNA replication timing alterations in genetic diseases
| PRJNA760942 | ENA
Project description:DNA replication timing alterations in genetic diseases
| PRJNA760943 | ENA
Project description:Cell fate change involves significant genome reorganization, including change in replication timing, but how these changes are related to genetic variation has not been examined. To study how change in replication timing that occurs during reprogramming impacts the copy number variation (CNV) landscape, we generated genome-wide replication timing profiles of induced pluripotent stem cells (iPSCs) and their parental fibroblasts. A significant portion of the genome changes replication timing as a result of reprogramming, indicative of overall genome reorganization. We found that early and late replicating domains in iPSCs are differentially affected by copy number gains and losses, and that in particular CNV gains accumulate in regions of the genome that change to earlier replication during the reprogramming process. This differential relationship was present irrespective of reprogramming method. Overall, our findings reveal a functional association between reorganization of replication timing and the CNV landscape that emerges during reprogramming. Keywords: Expression profiling by array [Gene expression] We isolated RNA from normal human fibroblast derived iPS cells, normal human fibroblasts, and human embryonic stem cells for hybridization to the Affymetrix gene expression microarrays. [CNV] We isolated genomic DNA from iPSCs derived with retroviral and episomal vectors and their parental fibroblast cells for hybridization to the Affymetrix Genome-Wide Human SNP 6.0 Array.
2014-03-28 | E-GEOD-55395 | biostudies-arrayexpress
Project description:DNA replication is spatially and temporally regulated during S-phase. DNA replication timing is established in early G1-phase at a point referred to as TDP (timing decision point). We show that Rif1 (Rap1-interacting-factor1), originally identified as a telomere binding factor in yeast, is a critical determinant of the replication timing program in human cells. Depletion of Rif1 results in specific loss of mid-S replication foci profiles, stimulation of initiation events in early S-phase and changes in long-range replication timing domain structures. Overall replication timing is shifted toward mid-S in both directions, suggesting that replication timing regulation is abrogated in the absence of Rif1. Rif1 tightly binds to nuclear insoluble structures at late-M to early-G1 and regulates the chromatin-loop sizes. Furthermore, Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early S-phase. Our results indicate that Rif1 plays crucial roles in determining the replication timing domain structures through regulating higher-order chromatin architecture. HeLa cells (ATCC), with a total of 4 individual replicates
2012-05-14 | E-GEOD-37971 | biostudies-arrayexpress
Project description:DNA methylation and DNA replication timing were examined across a variety of human tissues and cell lines, applying microarray-based techniques. The analyses revealed that late-replicating DNA was demethylated compared to the methylation of early-replicating regions.
2010-12-01 | GSE24947 | GEO
Project description:DNA methylation and DNA replication timing were examined across a variety of human tissues and cell lines, applying microarray-based techniques. The analyses revealed that late-replicating DNA was demethylated compared to the methylation of early-replicating regions.
2010-12-01 | GSE24947 | GEO
Project description:DNA replication is spatially and temporally regulated during S-phase. DNA replication timing is established in early G1-phase at a point referred to as TDP (timing decision point). We show that Rif1 (Rap1-interacting-factor1), originally identified as a telomere binding factor in yeast, is a critical determinant of the replication timing program in human cells. Depletion of Rif1 results in specific loss of mid-S replication foci profiles, stimulation of initiation events in early S-phase and changes in long-range replication timing domain structures. Overall replication timing is shifted toward mid-S in both directions, suggesting that replication timing regulation is abrogated in the absence of Rif1. Rif1 tightly binds to nuclear insoluble structures at late-M to early-G1 and regulates the chromatin-loop sizes. Furthermore, Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early S-phase. Our results indicate that Rif1 plays crucial roles in determining the replication timing domain structures through regulating higher-order chromatin architecture.
2012-05-15 | GSE37971 | GEO
Project description:In multicellular organisms, developmental changes to replication timing occur in 400- 800 kb domains across half the genome. While clear examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication timing has not been substantiated. To assess the role of DNA sequences in directing these changes, we profiled replication timing in mice carrying a genetically rearranged Human Chromosome 21 [Hsa21]. In two distinct mouse cell types, Hsa21 sequences maintained human-specific replication timing, except at points of Hsa21 rearrangement. Changes in replication timing at rearrangements extended up to 900 kb and consistently reconciled with the wild-type replication pattern at developmental boundaries of replication-timing domains. Our results demonstrate DNA sequencedriven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication timing regulation. Profile comparison of fibroblast and T-cell cultures from trans-chromosomic mice and human and mouse controls.
2012-06-04 | E-GEOD-38472 | biostudies-arrayexpress
Project description:Fused-in-sarcoma (FUS) encodes an RNA-binding protein with diverse roles in transcriptional activation and RNA splicing. While oncogenic fusions of FUS and transcription factor DNA-binding domains are associated with soft tissue sarcomas, dominant mutations in FUS cause amyotrophic lateral sclerosis (ALS). FUS has also been implicated in genome maintenance. However, the underlying mechanisms are unknown.
Here, we applied gene editing, functional reconstitution and integrated proteomic and transcriptomics to illuminate roles for FUS in DNA replication and repair. Consistent with a supportive role in DNA double-strand break (DSB) repair FUS deficient cells exhibited subtle alterations in the recruitment and retention of DSB-associated factors, including 53BP1 and BRCA1. FUS-/- cells also exhibited reduced proliferative potential that correlated with reduced replication fork speed, diminished loading of pre-replication complexes, enhanced micronucleus formation, and attenuated expression and splicing of S-phase associated genes. Finally, FUS-deficient cells exhibited genome-wide alterations in DNA replication timing that were reversed upon reeexpression of FUS cDNA. FUS-dependent replication domains were enriched in transcriptionally active chromatin and FUS was required for the timely replication of transcriptionally active DNA. These findings suggest that alterations DNA replication kinetics and programming contribute to genome instability and functional defects in FUS deficient cells.
2021-06-24 | MSV000087698 | MassIVE