Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [Hi-C]

ABSTRACT: Cohesin mediates sister chromatid cohesion and organizes the genome through the formation of chromatin loops. Two versions of the complex carrying either STAG1 or STAG2 show overlapping and specific functions and both are required to fulfill embryonic development. Cohesin-STAG1 displays longer residence time on chromatin that depends on CTCF and ESCO1 and establishes longer, long-lived chromatin loops together with CTCF. Cohesin-STAG2 shows a preferential interaction with WAPL and mediates shorter loops involved in tissue-specific transcription independently of CTCF. Here we show that the two variants respond in opposite ways to knock down of NIPBL, the putative cohesin loader that is also essential for loop extrusion. Cohesin-STAG1 levels increase on chromatin under this condition and the complex accumulates further at CTCF positions while cohesin-STAG2 is diminished genome-wide. Our data support a model in which NIPBL is not required for association of cohesin with chromatin but it is for loop extrusion, which in turn facilitates stabilization of cohesin-STAG2 at CTCF positions after being loaded elsewhere. In contrast, cohesin-STAG1 is preferentially loaded at CTCF sites independently of NIPBL. Nevertheless, loop formation by these chromatin-bound complexes is impaired and gene expression is severely affected, resembling alterations in Cornelia de Lange patients

ORGANISM(S): Homo sapiens

PROVIDER: GSE207115 | GEO | 2023/01/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [ChIP-Seq]

Project description:Cohesin mediates sister chromatid cohesion and organizes the genome through the formation of chromatin loops. Two versions of the complex carrying either STAG1 or STAG2 show overlapping and specific functions and both are required to fulfill embryonic development. Cohesin-STAG1 displays longer residence time on chromatin that depends on CTCF and ESCO1 and establishes longer, long-lived chromatin loops together with CTCF. Cohesin-STAG2 shows a preferential interaction with WAPL and mediates shorter loops involved in tissue-specific transcription independently of CTCF. Here we show that the two variants respond in opposite ways to knock down of NIPBL, the putative cohesin loader that is also essential for loop extrusion. Cohesin-STAG1 levels increase on chromatin under this condition and the complex accumulates further at CTCF positions while cohesin-STAG2 is diminished genome-wide. Our data support a model in which NIPBL is not required for association of cohesin with chromatin but it is for loop extrusion, which in turn facilitates stabilization of cohesin-STAG2 at CTCF positions after being loaded elsewhere. In contrast, cohesin-STAG1 is preferentially loaded at CTCF sites independently of NIPBL. Nevertheless, loop formation by these chromatin-bound complexes is impaired and gene expression is severely affected, resembling alterations in Cornelia de Lange patients

2023-01-30 | GSE207113 | GEO

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [RNA-Seq]

2023-01-30 | GSE207110 | GEO

ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin-STAG1 from WAPL

Project description:The human genome folds to create thousands of loops connecting sites that are bound by the insulator protein CTCF and the ring-shaped cohesin complex. It is thought that most of these loops emerge through a process whereby cohesin extrudes chromatin, forming an initially small loop that grows larger and larger until the loop’s expansion is arrested by CTCF. Cohesin rings comprise four proteins: SMC1, SMC3, SCC1, and, in higher eukaryotes, either STAG1 or STAG2. We explore differential roles of especially STAG1, STAG2 and ESCO1 proteins in chromatin organization.

2020-02-27 | GSE138405 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

Project description:Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer that is driven by the fusion transcription factor EWS-FLI1. We have integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicate that cohesin-STAG2 facilitates the communication between EWS-FLI1-bound long GGAA repeats acting as neoenhancers and their target promoters. Changes in CTCF-dependent chromatin contacts, unrelated to EWS-FLI1 binding, also contribute to the aggressive phenotype. STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, resulting in altered DNA looping dynamics. These results illuminate how STAG2 loss rewires the Ewing sarcoma chromatin interactome to promote metastasis and provide a list of potential biomarkers and therapeutic targets.

2024-09-18 | GSE267222 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267220 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267221 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [ChIP-seq]

Project description:Cohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer-promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate cohesin consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. To probe the physiological functions of cohesin, we created conditional knockout (cKO) mice with Stag2 deleted in the nervous system. Stag2 cKO mice exhibit growth retardation, neurological defects, and premature death, in part due to insufficient myelination of nerve fibers. Stag2 cKO oligodendrocytes exhibit delayed maturation and downregulation of myelinationrelated genes. Stag2 loss reduces promoter-anchored loops at downregulated genes in oligodendrocytes. Thus, STAG2-cohesin generates promoter-anchored loops at myelinationpromoting genes to facilitate their transcription. Our study implicates defective myelination as a contributing factor to cohesinopathy and establishes oligodendrocytes as a relevant cell type to explore the mechanisms by which cohesin regulates transcription.

2022-08-23 | GSE186891 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [Hi-C]

2022-08-23 | GSE186893 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [scRNA-seq]

2022-08-23 | GSE186892 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [RNA-seq]

2022-08-23 | GSE186890 | GEO