Cohesin and CTCF control chromosomal contact dynamics in living cells [integration sites]
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ABSTRACT:
PROVIDER: PRJNA809407 | ENA |
REPOSITORIES: ENA
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Project description:Mammalian chromosomes are partitioned into topologically associating domains (TADs) by the loop-extrusion activity of cohesin that is blocked at specific DNA sites bound by CTCF. Chromosome structure inside TADs is highly variable in single cells, yet little is known about its temporal dynamics, how it influences the rates and durations of chromosomal contacts, and how it depends on CTCF and cohesin. To address these questions we combine two quantitative live-cell imaging strategies that minimize locus-specific confounding effects. We show that loop extrusion by cohesin globally reduces the mobility of the chromatin fiber in living cells, while also increasing the rates of formation and durations of contacts between sequences inside the same TAD. Quantitative analysis of high-resolution microscopy data reveals that contacts assemble and disassemble frequently in the course of the cell cycle, and become substantially more frequent and longer in the presence of convergent CTCF sites. Comparison with polymer modeling additionally reveals that cohesin-mediated CTCF loops last around 10 minutes on average. Our data support the notion that chromosome structure within TADs is highly dynamic and provide a quantitative framework for understanding the principles that link chromosome structure to biological function.
2022-02-27 | GSE197237 | GEO
Project description:Cohesin and CTCF control chromosomal contact dynamics in living cells
| PRJNA809409 | ENA
Project description:Mammalian chromosomes are partitioned into topologically associating domains (TADs) by the loop-extrusion activity of cohesin that is blocked at specific DNA sites bound by CTCF. Chromosome structure inside TADs is highly variable in single cells, yet little is known about its temporal dynamics, how it influences the rates and durations of chromosomal contacts, and how it depends on CTCF and cohesin. To address these questions we combine two quantitative live-cell imaging strategies that minimize locus-specific confounding effects. We show that loop extrusion by cohesin globally reduces the mobility of the chromatin fiber in living cells, while also increasing the rates of formation and durations of contacts between sequences inside the same TAD. Quantitative analysis of high-resolution microscopy data reveals that contacts assemble and disassemble frequently in the course of the cell cycle, and become substantially more frequent and longer in the presence of convergent CTCF sites. Comparison with polymer modeling additionally reveals that cohesin-mediated CTCF loops last around 10 minutes on average. Our data support the notion that chromosome structure within TADs is highly dynamic and provide a quantitative framework for understanding the principles that link chromosome structure to biological function.
2022-02-27 | GSE197234 | GEO
Project description:Mammalian chromosomes are partitioned into topologically associating domains (TADs) by the loop-extrusion activity of cohesin that is blocked at specific DNA sites bound by CTCF. Chromosome structure inside TADs is highly variable in single cells, yet little is known about its temporal dynamics, how it influences the rates and durations of chromosomal contacts, and how it depends on CTCF and cohesin. To address these questions we combine two quantitative live-cell imaging strategies that minimize locus-specific confounding effects. We show that loop extrusion by cohesin globally reduces the mobility of the chromatin fiber in living cells, while also increasing the rates of formation and durations of contacts between sequences inside the same TAD. Quantitative analysis of high-resolution microscopy data reveals that contacts assemble and disassemble frequently in the course of the cell cycle, and become substantially more frequent and longer in the presence of convergent CTCF sites. Comparison with polymer modeling additionally reveals that cohesin-mediated CTCF loops last around 10 minutes on average. Our data support the notion that chromosome structure within TADs is highly dynamic and provide a quantitative framework for understanding the principles that link chromosome structure to biological function.
2022-02-27 | GSE197231 | GEO
Project description:Mammalian chromosomes are partitioned into topologically associating domains (TADs) by the loop-extrusion activity of cohesin that is blocked at specific DNA sites bound by CTCF. Chromosome structure inside TADs is highly variable in single cells, yet little is known about its temporal dynamics, how it influences the rates and durations of chromosomal contacts, and how it depends on CTCF and cohesin. To address these questions we combine two quantitative live-cell imaging strategies that minimize locus-specific confounding effects. We show that loop extrusion by cohesin globally reduces the mobility of the chromatin fiber in living cells, while also increasing the rates of formation and durations of contacts between sequences inside the same TAD. Quantitative analysis of high-resolution microscopy data reveals that contacts assemble and disassemble frequently in the course of the cell cycle, and become substantially more frequent and longer in the presence of convergent CTCF sites. Comparison with polymer modeling additionally reveals that cohesin-mediated CTCF loops last around 10 minutes on average. Our data support the notion that chromosome structure within TADs is highly dynamic and provide a quantitative framework for understanding the principles that link chromosome structure to biological function.
2022-02-27 | GSE197226 | GEO
Project description:Cohesin and CTCF control chromosomal contact dynamics in living cells [4C-seq]
| PRJNA809391 | ENA
Project description:Cohesin and CTCF control chromosomal contact dynamics in living cells [Hi-C]
| PRJNA809402 | ENA
Project description:Cohesin and CTCF control chromosomal contact dynamics in living cells [capture C]
| PRJNA809406 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-27 | GSE197238 | GEO
Project description:Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.
| EGAS00001003010 | EGA