Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcription control (RNA-Seq)

ABSTRACT: Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A and RAD21, cohesin contains in somatic cells one of two orthologous STAG subunits, SA1 or SA2. How these variable subunits affect the function of the cohesin complex is still unclear. SA1- and SA2-cohesin were initially proposed to organize cohesion at telomeres and centromeres, respectively. Here, we uncover redundant and specific roles of SA1 and SA2 in gene regulation and chromatin looping using HCT116 cells with an auxin-inducible degron (AID) tag fused to either SA1 or SA2. Following rapid depletion of either subunit, we perform high resolution Hi-C, RNA-sequencing and sequential ChIP studies to show that SA1 and SA2 do not co-occupy individual binding sites and have distinct ways how they affect looping and gene expression. These findings are supported at the single cell level by single-molecule localizations via dSTORM super-resolution imaging. Since somatic and congenital mutations of the SA subunits are associated with cancer (SA2) and intellectual disability syndromes with congenital abnormalities (SA1 and SA2), we verified SA1-/SA2-dependencies using human neural stem cells, hence highlighting their importance for understanding particular disease contexts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133022 | GEO | 2020/03/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcription control (Hi-C)

Project description:Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A and RAD21, cohesin contains in somatic cells one of two orthologous STAG subunits, SA1 or SA2. How these variable subunits affect the function of the cohesin complex is still unclear. SA1- and SA2-cohesin were initially proposed to organize cohesion at telomeres and centromeres, respectively. Here, we uncover redundant and specific roles of SA1 and SA2 in gene regulation and chromatin looping using HCT116 cells with an auxin-inducible degron (AID) tag fused to either SA1 or SA2. Following rapid depletion of either subunit, we perform high resolution Hi-C, RNA-sequencing and sequential ChIP studies to show that SA1 and SA2 do not co-occupy individual binding sites and have distinct ways how they affect looping and gene expression. These findings are supported at the single cell level by single-molecule localizations via dSTORM super-resolution imaging. Since somatic and congenital mutations of the SA subunits are associated with cancer (SA2) and intellectual disability syndromes with congenital abnormalities (SA1 and SA2), we verified SA1-/SA2-dependencies using human neural stem cells, hence highlighting their importance for understanding particular disease contexts.

2020-03-06 | GSE133023 | GEO

Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcription control (ChIP-Seq)

2020-03-06 | GSE133021 | GEO

Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcription control (ChiP-Seq 2)

Project description:Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A and RAD21, cohesin contains in somatic cells one of two orthologous STAG subunits, STAG1 or STAG2. How these variable subunits affect the function of the cohesin complex is still unclear. STAG1- and STAG2-cohesin were initially proposed to organize cohesion at telomeres and centromeres, respectively. Here, we uncover redundant and specific roles of STAG1 and STAG2 in gene regulation and chromatin looping using HCT116 cells with an auxin-inducible degron (AID) tag fused to either STAG1 or STAG2. Following rapid depletion of either subunit, we perform high resolution Hi-C, RNA-sequencing and sequential ChIP studies to show that STAG1 and STAG2 do not co-occupy individual binding sites and have distinct ways how they affect looping and gene expression. These findings are supported at the single cell level by single-molecule localizations via dSTORM super-resolution imaging. Since somatic and congenital mutations of the STAG subunits are associated with cancer (STAG2) and intellectual disability syndromes with congenital abnormalities (STAG1 and STAG2), we verified STAG1-/STAG2-dependencies using human neural stem cells, hence highlighting their importance for understanding particular disease contexts.

2020-03-06 | GSE140751 | GEO

Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization

Project description:In addition to mediating sister chromatid cohesion, cohesin plays a central role in DNA looping and segmentation of the genome into contact domains (TADs). Two variant cohesin complexes that contain either STAG/SA1 or SA2 are present in all cell types. Here we addressed their specific contribution to genome architecture in non-transformed human cells. We found that cohesin-SA1 drives stacking of cohesin rings at CTCF-bound sites and thereby contributes to the stabilization and preservation of TAD boundaries. In contrast, a more dynamic cohesin-SA2 promotes cell type-specific contacts between enhancers and promoters within TADs independently of CTCF. SA2 loss, a condition frequently observed in cancer cells, results in increased intra-TAD interactions, likely altering the expression of key cell identity genes.

2018-05-31 | GSE101921 | GEO

A unique role of Cohesin-SA1 in gene regulation and development [ChIP-Seq]

Project description:Vertebrates have two cohesin complexes that consist of Smc1, Smc3, Rad21/Scc1 and either SA1 or SA2, but their functional specificity is unclear. Mouse embryos lacking SA1 show developmental delay and die before birth. Comparison of the genome wide distribution of cohesin in wild-type and SA1-null cells reveals that SA1 is largely responsible for cohesin accumulation at promoters and at sites bound by the insulator protein CTCF. As a consequence, ablation of SA1 alters transcription of genes involved in biological processes related to Cornelia de Lange syndrome (CdLS), a genetic disorder linked to dysfunction of cohesin. We show that the presence of cohesin-SA1 at the promoter of myc and of protocadherin genes positively regulates their expression, a task that cannot be assumed by cohesin-SA2. Cohesin binding pattern along some gene clusters is also affected by the lack of SA1, leading to dysregulation of the genes within. We hypothesize that impaired cohesin-SA1 function in gene expression underlies the molecular etiology of CdLS. Examination of genome wide distribution of cohesin subunits in wildtype and SA1-null cells

2012-03-15 | E-GEOD-32319 | biostudies-arrayexpress

A unique role of Cohesin-SA1 in gene regulation and development [Expression]

Project description:Vertebrates have two cohesin complexes that consist of Smc1, Smc3, Rad21/Scc1 and either SA1 or SA2, but their functional specificity is unclear. Mouse embryos lacking SA1 show developmental delay and die before birth. Comparison of the genome wide distribution of cohesin in wild-type and SA1-null cells reveals that SA1 is largely responsible for cohesin accumulation at promoters and at sites bound by the insulator protein CTCF. As a consequence, ablation of SA1 alters transcription of genes involved in biological processes related to Cornelia de Lange syndrome (CdLS), a genetic disorder linked to dysfunction of cohesin. We show that the presence of cohesin-SA1 at the promoter of myc and of protocadherin genes positively regulates their expression, a task that cannot be assumed by cohesin-SA2. Cohesin binding pattern along some gene clusters is also affected by the lack of SA1, leading to dysregulation of the genes within. We hypothesize that impaired cohesin-SA1 function in gene expression underlies the molecular etiology of CdLS. Two-condition experiment, SA1 KO vs. WT cells. 3 Biological replicates.

2012-03-15 | E-GEOD-32234 | biostudies-arrayexpress

A unique role of Cohesin-SA1 in gene regulation and development [ChIP-Seq]

2012-03-15 | GSE32319 | GEO

A unique role of Cohesin-SA1 in gene regulation and development [Expression]

2012-03-15 | GSE32234 | GEO

The contribution of cohesin-SA1 to chromatin architecture and gene expression in two murine tissues [RNA-seq]

Project description:Cohesin, which consists of SMC1, SMC3, Rad21 and either SA1 or SA2, topologically embraces the chromatin fibers to hold sister chromatids together and to stabilize chromatin loops. Increasing evidence indicates that these loops are the organizing principle of higher-order chromatin architecture, which in turn is critical for gene expression. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these are enriched at the regulatory regions of tissue-specific genes. Cohesin colocalizes extensively with the CCCTC-binding factor (CTCF). Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1 whereas either cohesin-SA1 or cohesin-SA2 are present at active promoters independently of CTCF. Analyses of chromatin contacts at the Protocadherin gene cluster and the Regenerating islet-derived (Reg) gene cluster, mostly expressed in brain and pancreas respectively, revealed remarkable differences in the architecture of these loci in the two tissues that correlate with the presence of cohesin. Moreover, we found decreased binding of cohesin and reduced transcription of the Reg genes in the pancreas of SA1 heterozygous mice. Given that Reg proteins are involved in the control of inflammation in pancreas, such reduction may contribute to the increased incidence of pancreatic cancer reported in these animals. Examination of the relationship between gene expression, genome wide cohesin distribution and chromatin structure

2015-04-07 | E-GEOD-59119 | biostudies-arrayexpress

Somatic mutation of the cohesin complex subunit confers therapeutic vulnerabilities in human cancer

Project description:Synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor suppressor gene mutations, as exemplified by the effectiveness of poly(ADP)-ribose polymerase (PARP) inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental housekeeping functions in the cell. Here we explore an approach to identify the “essential lethality” arose from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy. In additional to the known synthetic-lethal interactions, this approach uncovered the cohesion subunit SA1 as a putative synthetic-essential target in cancers carrying inactivating mutations of its paralog, SA2. In SA2-deficient Ewing sarcoma and bladder cancers, further depletion of SA1 profoundly and specifically suppressed cancer cell proliferation, survival and tumorigenic potential. Mechanistically, inhibition of SA1 in the SA2-mutated cells leads to premature chromatid separation and dramatic extension of mitotic duration, which is accompanied by lethal failure of cell division. More importantly, depletion of SA1 renders those SA2-mutated cells not only more susceptible to DNA damage, especially double-strand breaks (DSBs), but also defective in DNA repair. Furthermore, inhibition of SA1 sensitizes the SA2-deficient cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with SA2-deficient tumors. This study provides a framework for the discovery of therapeutic targets in cancers that harbor specific essential gene deficiency.

2021-02-22 | GSE111004 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data