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Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE277721 | GEO | 2024/10/07

REPOSITORIES: GEO

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Similar Datasets

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [ChIP-seq]

Project description:The organization of the genome in three-dimensional space is highly dynamic, yet how these dynamics are regulated and the role they play in genome function is poorly understood. Here, we utilized acute depletion of NIPBL to characterize the role of cohesin-mediated loop extrusion in vivo. Using this approach, we find that many chromatin loops are rapidly diminished upon loss of NIBPL, consistent with recent single locus imaging studies showing that chromatin loops are transient. However, we also identified a subset of cohesin-dependent chromatin loops that are anchored in repressive chromatin and may be “long-lived”, given that they require NIPBL for their establishment upon mitotic exit, but are persistent when NIPBL is depleted from interphase cells. In addition to the reformation of 3D genome structures, mitotic exit coincides with widespread transcriptional activation. We found that NIPBL is essential for establishing the expression of lineage-defining genes during the M-G1 transition but has diminished impact in the steady-state maintenance of their expression. At genes sensitive to its depletion, NIPBL supports a unique local genome organization defined by greater spatial proximity to nearby enhancers and weaker transcription start site insulation of genomic contacts. Overall, we show that NIPBL-mediated loop extrusion is critical to genome organization and transcriptional regulation in vivo.

2024-10-07 | GSE277720 | GEO

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [Hi-C]

2024-10-07 | GSE277719 | GEO

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [SLAM-seq]

2024-10-07 | GSE277898 | GEO

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation

Project description:Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation

| PRJNA1163536 | ENA

Universal dynamics of cohesin-mediated loop extrusion

Project description:Most animal genomes are partitioned into Topologically Associating Domains (TADs), created by cohesin-mediated loop extrusion and defined by convergently oriented CTCF sites. The dynamics of loop extrusion and its regulation remains poorly characterized in vivo. Here, we tracked TAD anchors in living human cells to visualize and quantify cohesin-dependent loop extrusion across multiple endogenous genomic regions. We show that TADs are dynamic structures whose anchors are brought in proximity about once per hour and for 6-19 min (~16% of the time). TADs are continuously subjected to extrusion by multiple cohesin complexes, extruding loops at ~0.1 kb/s. Remarkably, despite strong differences of Hi-C patterns between the chromatin regions, their dynamics is consistent with the same density, residence time and speed of cohesin. Our results suggest that TAD dynamics is governed primarily by CTCF site location and affinity, which allows genome-wide predictive models of cohesin-dependent interactions.

2024-07-28 | GSE273257 | GEO

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [SLAM-seq]

Project description:Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [SLAM-seq]

| PRJNA1164730 | ENA

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [Hi-C]

Project description:Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [Hi-C]

| PRJNA1163538 | ENA

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [ChIP-seq]

Project description:Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [ChIP-seq]

| PRJNA1163540 | ENA

Universal dynamics of cohesin-mediated loop extrusion

Project description:Universal dynamics of cohesin-mediated loop extrusion

| PRJNA1140881 | ENA

MCM complexes are barriers that restrict cohesin-mediated loop extrusion.

Project description:Eukaryotic genomes are compacted into loops and topologically associating domains (TADs)1-3, which contribute to transcription, recombination and genomic stability4,5. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered6-12. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, which suggests that loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, in which MCMs affect the number of CTCF-anchored loops and gene expression. Simulations suggest that MCMs are abundant, randomly positioned and partially permeable barriers. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Notably, chimeric yeast MCMs that contain a cohesin-interaction motif from human MCM3 induce cohesin pausing, indicating that MCMs are 'active' barriers with binding sites. These findings raise the possibility that cohesin can arrive by loop extrusion at MCMs, which determine the genomic sites at which sister chromatid cohesion is established. On the basis of in vivo, in silico and in vitro data, we conclude that distinct loop extrusion barriers shape the three-dimensional genome.

| S-EPMC9159944 | biostudies-literature

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