Genome Organization Drives Chromosome Fragility
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA387539 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome Organization Drives Chromosome Fragility [ChIP-seq]
| PRJNA387544 | ENA
Project description:Genome Organization Drives Chromosome Fragility [END-seq]
| PRJNA387545 | ENA
Project description:In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT.
| S-EPMC6133249 | biostudies-literature
Project description:In this study, we show that evolutionarily conserved chromosome loop anchors bound by CTCF and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy concomitantly rewire DNA cleavage sites to novel contact domain boundaries. While transcription and replication coupled genomic rearrangements have been well documented, we demonstrate that DSBs at loop anchors are transcription-, replication-, and cell type- independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in acute leukemias and prostate cancers. Thus, loop anchors serve as preferred and promiscuous fragile sites that generate DSBs and chromosomal rearrangements.
2017-06-28 | GSE99194 | GEO
Project description:In this study, we show that evolutionarily conserved chromosome loop anchors bound by CTCF and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy concomitantly rewire DNA cleavage sites to novel contact domain boundaries. While transcription and replication coupled genomic rearrangements have been well documented, we demonstrate that DSBs at loop anchors are transcription-, replication-, and cell type- independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in acute leukemias and prostate cancers. Thus, loop anchors serve as preferred and promiscuous fragile sites that generate DSBs and chromosomal rearrangements.
2017-06-28 | GSE99196 | GEO
Project description:In this study, we show that evolutionarily conserved chromosome loop anchors bound by CTCF and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy concomitantly rewire DNA cleavage sites to novel contact domain boundaries. While transcription and replication coupled genomic rearrangements have been well documented, we demonstrate that DSBs at loop anchors are transcription-, replication-, and cell type- independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in acute leukemias and prostate cancers. Thus, loop anchors serve as preferred and promiscuous fragile sites that generate DSBs and chromosomal rearrangements.
2017-06-28 | GSE99195 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-28 | GSE99197 | GEO
Project description:Metaphase-Chromosome-Organization
| PRJEB4743 | ENA
Project description:Genome Organization Drives Chromosome Fragility [nsRNA-seq]
| PRJNA387543 | ENA
Project description:Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two alternative three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell-type-specific organization described previously for non-synchronous cells is restricted to interphase. In metaphase, we identify a homogenous folding state, which is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we find that metaphase Hi-C data is inconsistent with classic hierarchical models, and is instead best described by a linearly-organized longitudinally compressed array of consecutive chromatin loops.
2013-11-05 | E-MTAB-1948 | biostudies-arrayexpress