Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101921 | GEO | 2018/05/31
REPOSITORIES: GEO
Similar Datasets
Project description:Cohesin complex, a main organizer of mammalian genomes, exists in two versions that differ in the identity of the STAG/SA subunit, which can be SA1 or SA2. Mouse embryonic stem cell (mESC) provide a useful system to address the specific contributions of each variant to genome architecture and gene expression, since 3D organization of super- enhancers and Polycomb domains is essential to achieve transcription of pluripotency factors and repression of lineage specification genes, respectively. Hi-C analyses reveal That cohesin-SA1 preserves the integrity of topological associating domains (TAD) boundaries together with CTCF and prevents excessive segregation of same-class Compartment regions. Cohesin-SA2 is enriched within super-enhancers and Polycomb domains. Moreover, it contributes to establishment and compaction of Polycomb domains through PRC1 recruitment thereby promoting interchromosomal interactions among Hox gene promoters and favoring gene repression. In contrast, these interactions are counteracted by cohesin-SA1. The opposite effects of the two complexes on genome topology explain the distinct consequences of their ablation for the mESCs Transcriptome.
2019-06-18 | GSE126659 | GEO
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
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
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.
2012-03-15 | GSE32234 | GEO
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.
2012-03-15 | GSE32319 | GEO
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
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.
2015-04-07 | GSE59119 | GEO
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 | GSE133022 | GEO
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
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 | GSE133021 | GEO