Cohesin interacts with a panoply of splicing factors required for cell cycle progression and genomic organization
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471704 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Here we report that endogenous human cohesin interacts with a panoply of splicing factors and RNA binding proteins, including diverse components of the U4/U6.U5 tri-snRNP complex and several splicing factors that are commonly mutated in cancer. The interactions are enhanced during mitosis, and the interacting splicing factors and RNA binding proteins follow the cohesin cycle and prophase pathway of regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors results in stereotyped cell cycle arrests and alterations in genomic organization. These data support the hypothesis that splicing factors and RNA binding proteins control cell cycle progression and genomic organization via regulated interactions with cohesin and chromatin.
2018-05-17 | GSE114539 | GEO
Project description:Embryonic stem cells (ESCs) cells run a self-renewal gene expression program, requiring the expression of certain transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs remains enigmatic. Here we show that Cohesin exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of the cohesin subunit Rad21 reveal an ESC specific cohesin binding pattern that is characterized by a CTCF independent colocalization of cohesin with pluripotency related transcription factors. Upon ESC differentiation, these binding sites disappear and instead new CTCF independent Rad21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of cohesin subunits causes expression changes that are reminiscent of the depletion of key pluripotency transcription factors, demonstrating the functional relevance of the cohesin - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin interacting proteins Stag1 and Wapl, further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-05-19 | E-GEOD-24030 | biostudies-arrayexpress
Project description:CTCF sites are abundant in the genomes of diverse species but their function is enigmatic. We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the β-globin locus and flanking olfactory receptor genes. Although CTCF occupies these sites in both erythroid K562 cells and fibroblast 293T cells, the long-range interaction frequencies among the sites are highly cell type specific, revealing a more densely clustered organization in the absence of globin gene activity. Both CTCF and cohesins are required for the cell-type-specific chromatin conformation. Furthermore, loss of the organizational loops in K562 cells through reduction of CTCF with shRNA results in acquisition of repressive histone marks in the globin locus and reduces globin gene expression, whereas silent flanking olfactory receptor genes are unaffected. These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function. Comparison of CTCF binding in K562 and 293T cells using ChIP-chip. 3 replicates each cell type, ChIP and input DNA for each replicate.
2011-01-13 | E-GEOD-26507 | biostudies-arrayexpress
Project description:Cohesin Regulates 3D Accessible Genome Organization and Function
| PRJNA603822 | ENA
Project description:Cohesin organizes mammalian interphase chromosomes by reeling chromatin fibers into dynamic loops. "Loop extrusion" is obstructed when cohesin encounters a properly oriented CTCF protein. It has been proposed that transcription relocalizes or interferes with cohesin, and that active transcription start sites function as cohesin loading sites, but how these effects, and transcription in general, shape chromatin is unknown. To determine whether transcription can modulate loop extrusion, we studied cells in which the primary extrusion barriers could be removed by CTCF depletion and cohesin’s residence time and abundance on chromatin could be increased by Wapl knockout. We found evidence that transcription directly interacts with loop extrusion through a novel "moving barrier" mechanism, but not by loading cohesin at active promoters. Hi-C experiments showed intricate, cohesin-dependent genomic contact patterns near actively transcribed genes, and in CTCF-Wapl double knockout (DKO) cells, genomic contacts were enriched between sites of transcription-driven cohesin localization ("cohesin islands"). Similar patterns also emerged in polymer simulations in which transcribing RNA polymerases (RNAPs) acted as "moving barriers" by impeding, slowing, or pushing loop-extruding cohesins. The model predicts that cohesin does not load preferentially at promoters and instead accumulates at TSSs due to the barrier function of RNAPs. We tested this prediction by new ChIP-seq experiments, which revealed that the "cohesin loader" Nipbl co-localizes with cohesin, but, unlike in previous reports, Nipbl did not accumulate at active promoters. We propose that RNAP acts as a new type of barrier to loop extrusion that, unlike CTCF, is not stationary in its precise genomic position, but is itself dynamically translocating and relocalizes cohesin along DNA. In this way, loop extrusion could enable translocating RNAPs to maintain contacts with distal regulatory elements, allowing transcriptional activity to shape genomic functional organization.
2023-03-13 | GSE196621 | GEO
Project description:The three-dimensional organization of chromosomes is tightly related to their biological function. Both imaging and chromosome conformation capture studies have revealed several layers of organization, including segregation into active and inactive compartments at the megabase scale, and partitioning into domains (TADs) and associated loops at the sub-megabase scale. Yet, it remains unclear how these layers of genome organization form, interact with one another, and contribute to or result from genome activities. TADs seem to have critical roles in regulating gene expression by promoting or preventing interactions between promoters and distant cis-acting regulatory elements, and different architectural proteins, including cohesin, have been proposed to play central roles in their formation. But so far, experimental depletions of these proteins have resulted in marginal changes in chromosome organization. Here, we show that deletion of the cohesin-loading factor, Nipbl, leads to loss of chromosome-associated cohesin and results in dramatic genome reorganization. TADs and associated loops vanish globally, even in the absence of transcriptional changes. In contrast, segregation into compartments is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the 3D organization of the genome results from the independent action of two distinct mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartment regions, defined by the underlying chromatin state; and 2) cohesin-dependent formation of TADs possibly by the recently proposed loop extrusion mechanism, enabling long-range and target-specific activity of promiscuous enhancers. The interplay between these mechanisms creates an architecture that is more complex than a simple structural hierarchy and can be central to guiding normal development.
2017-06-10 | GSE93431 | GEO
Project description:The functions of cohesin are central to genome integrity, chromosome organization, and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex, however, little is known about how it stimulates the cohesin loading activity. Here we determine the large “hook” structure of Scc2 responsible for catalyzing cohesin loading. We identify key Scc2 surfaces that are crucial for DNA binding and for cohesin loading in vivo. Using previously determined structures and modeling, we derive a pseudo-atomic structure of the full-length Scc2-Scc4 complex. Finally, our crosslinking and electron microscopy analyses reveal that Scc2-Scc4 utilizes its modular structure to make multiple contacts with a folded cohesin at an interface created by the cohesin head-hinge interaction.
2017-01-11 | PXD004692 | Pride
Project description:CTCF is present at the anchors of thousands of loops likely formed via cohesin-mediated loop extrusion in mammalian cells. Interaction domains present in D. melanogaster chromosomes form via the segregation of active and inactive chromatin in the absence of CTCF looping, but the role of transcription versus other architectural proteins in chromatin organization is unclear. Here we find that positioning of RNAPII via transcription elongation is essential in the formation of gene loops, which in turn interact to form compartmental domains. Inhibition of transcription elongation or depletion of cohesin decreases gene looping and formation of active compartmental domains. In contrast, depletion of condensin II, which also localizes to active chromatin, results in increased gene looping, formation of compartmental domains, and stronger intra-chromosomal compartmental interactions. Condensin II has a similar role in maintaining inter-chromosomal interactions responsible for pairing between homologous chromosomes, whereas inhibition of transcription elongation or cohesin depletion has little effect on homolog pairing. The results suggest distinct roles for cohesin and condensin II in the establishment of 3D nuclear organization in Drosophila.
2019-03-11 | GSE118756 | GEO
Project description:The cohesin complex plays essential roles in sister chromatin cohesin, chromosome organization and gene expression. The role it plays in the regulation of genes is incompletely understood. Here, we report that the cohesin release factor WAPL in mouse embryonic stem cells is crucial for maintaining a pool of dynamically bound cohesin to regions in the genome that are associated with lineage specific genes. These regions are enriched for active enhancer marks and transcription factor binding sites. Stabilization of cohesin, which leads to a loss of dynamic cohesin from these regions does not affect transcription factor binding or active enhancer marks, but does result in changes in promoter-enhancer interactions and downregulation of genes. Acute cohesin depletion can phenocopy the effect of WAPL depletion, showing that cohesin plays a crucial role in maintaining expression of lineage specific genes. The binding of dynamic cohesin to chromatin is dependent on the pluripotency transcription factor OCT4, but not NANOG. Finally, sites of dynamic cohesin binding sites are also found in differentiated cells, suggesting that they represent a general regulatory principle. We propose that the binding of dynamic cohesin to regulatory sites creates a favorable spatial environment in which promoters and enhancers can communicate to ensure proper gene expression.
2020-10-15 | GSE135180 | GEO
Project description: Not available
| S-EPMC3578776 | biostudies-literature