LATS kinase-mediated selective disruption of CTCF genomic binding
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114319 | GEO | 2020/03/09
REPOSITORIES: GEO
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Project description:LATS kinase-mediated selective disruption of CTCF genomic binding
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Project description:LATS regulates heavy metal response
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Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. ChIP-seq data from naive and primed human embroynic stem cells.
2015-11-22 | E-GEOD-69646 | biostudies-arrayexpress
Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. Polyadenylated RNA-seq from naive and primed human embroynic stem cells.
2015-11-22 | E-GEOD-69692 | biostudies-arrayexpress
Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. ChIA_PET data against SMC1 from naive and primed human embroynic stem cells.
2015-11-22 | E-GEOD-69643 | biostudies-arrayexpress
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE92931 | GEO
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE92587 | GEO
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE97803 | GEO
Project description:NDR/LATS kinases regulate multiple aspects of cell polarity and morphogenesis from yeast to mammals, but few of their substrates are known. Fission yeast NDR/LATS kinase Orb6 has been proposed to control cell polarity via spatial regulation of Gef1, a guanine nucleotide exchange factor for the small GTPase Cdc42. Here we show that Orb6 plays a critical role as a positive regulator of exocytosis, independent of Gef1. Through Orb6 inhibition in vivo and quantitative global phosphoproteomics, we identify several proteins involved in membrane trafficking as Orb6 targets, and we confirm Sec3 and Sec5, conserved components of the exocyst complex, as substrates of Orb6 both in vivo and in vitro. Our results suggest that Orb6 kinase activity is crucial for exocyst localization to actively-growing cell tips and for exocyst activity during septum dissolution after cytokinesis. We further show that Orb6 phosphorylation of Sec3 serine-201 contributes to exocyst function in parallel with exocyst protein Exo70. We propose that Orb6 contributes to polarized growth by regulating membrane trafficking at multiple levels.
2019-01-31 | PXD009408 | Pride
Project description:Although the chromatin regulator CTCF is enriched at genes escaping from X-chromosome inactivation (XCI), molecular mechanisms remain elusive. We examined CTCF and epigenetic features at escape genes on the inactive X (Xi) in mouse F1 hybrid cells and tissues. We found that escape genes are located inside topologically insulated domains limited by convergent arrays of CTCF binding sites, suggesting loop formation. Xi-specific deletion of a CTCF right boundary of the escape gene Car5b caused loss of CTCF binding and changes of histone modifications at Car5b and abolished escape, suggesting loss of insulation. This is consistent with Car5b lack of escape in mouse brain showing no CTCF binding at the boundary. Inversion of this boundary had no effect on Car5b escape, suggesting that tandem coiled looping could still function as insulation. To test whether chromatin features of the Xi could affect escape we examined mutants in which the Xi-specific compact structure is disrupted or there is loss of H3K27me3 enrichment. We found that both conditions cause an Xi-specific increase in active marks and gene expression at escape regions, suggesting that the 3D structure and heterochromatic marks of the Xi play a role in modulating escape levels of genes insulated by CTCF.
2023-05-18 | GSE231626 | GEO