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Transcription-mediated supercoiling regulates genome folding and loop formation

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE169492 | GEO | 2021/07/22

REPOSITORIES: GEO

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Similar Datasets

Transcription-mediated supercoiling regulates genome folding and loop formation.

Project description:The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top of the loops and is physically segregated from cohesin. Augmented looping upon increased loading of cohesin on chromosomes causes disruption of Lamin at the nuclear rim and chromatin blending, a homogeneous distribution of chromatin within the nucleus. Altering supercoiling via either transcription or topoisomerase inhibition counteracts chromatin blending, increases chromatin condensation, disrupts loop formation, and leads to altered cohesin distribution and mobility on chromatin. Overall, negative supercoiling generated by transcription is an important regulator of loop formation in vivo.

| S-EPMC9482096 | biostudies-literature

Transcription-mediated supercoiling regulates genome folding and loop formation [RNA-Seq]

Project description:The chromatin fiber folds into loops, however the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualized that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top of the loops and is physically segregated from cohesin. Augmented looping upon increased loading of cohesin on chromosomes causes disruption of Lamin at the nuclear rim and chromatin blending, a homogenous distribution of chromatin within the nucleus. Altering supercoiling via either transcription or topoisomerase inhibition counteracts chromatin blending, increases chromatin condensation, disrupts loop formation and leads to altered cohesin distribution and mobility on chromatin. Overall, negative supercoiling generated by transcription is an important regulator of loop formation in vivo.

2021-07-22 | GSE169476 | GEO

Transcription-mediated supercoiling regulates genome folding and loop formation [ChIP-Seq]

2021-07-22 | GSE169474 | GEO

Transcription-mediated supercoiling regulates genome folding and loop formation

Project description:Transcription-mediated supercoiling regulates genome folding and loop formation

| PRJNA716693 | ENA

Transcription-mediated supercoiling regulates genome folding and loop formation [RNA-Seq]

Project description:Transcription-mediated supercoiling regulates genome folding and loop formation [RNA-Seq]

| PRJNA716691 | ENA

Transcription-mediated supercoiling regulates genome folding and loop formation [ChIP-Seq]

Project description:Transcription-mediated supercoiling regulates genome folding and loop formation [ChIP-Seq]

| PRJNA716665 | ENA

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells

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

2021-11-04 | GSE167020 | GEO

m6A facilitates transcription termination by promoting R-loop formation

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

2019-10-15 | GSE134964 | GEO

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes.

Project description:Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders. Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites. We discuss the role of supercoiling in stimulating enhancer promoter contacts and propose that transcription of eRNA sends the first wave of supercoiling that can activate mRNA transcription in a given TAD.

| S-EPMC5829651 | biostudies-literature

Supercoiling-mediated feedback rapidly couples and tunes transcription.

Project description:Transcription induces a wave of DNA supercoiling, altering the binding affinity of RNA polymerases and reshaping the biochemical landscape of gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes the regulation of proximal genes, forming a complex feedback loop. However, a theoretical framework is needed to integrate biophysical regulation with biochemical transcriptional regulation. To investigate the role of supercoiling-mediated feedback within multi-gene systems, we model transcriptional regulation under the influence of supercoiling-mediated polymerase dynamics, allowing us to identify patterns of expression that result from physical inter-gene coupling. We find that gene syntax-the relative ordering and orientation of genes-defines the expression profiles, variance, burst dynamics, and inter-gene correlation of two-gene systems. Furthermore, supercoiling can enhance or weaken biochemical regulation. Our results suggest that supercoiling couples behavior between neighboring genes, providing a regulatory mechanism that tunes transcriptional variance in engineered gene networks and explains the behavior of co-localized native circuits.

| S-EPMC9624111 | biostudies-literature

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