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• W3130485834 abstract "Abstract Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity." @default.
• W3130485834 created "2021-03-01" @default.
• W3130485834 creator A5011491497 @default.
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• W3130485834 creator A5075099532 @default.
• W3130485834 date "2021-02-19" @default.
• W3130485834 modified "2023-10-17" @default.
• W3130485834 title "Functional impact of cancer-associated cohesin variants on gene expression and cellular identity" @default.
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• W3130485834 doi "https://doi.org/10.1093/genetics/iyab025" @default.
• W3130485834 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8049558" @default.
• W3130485834 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33704438" @default.
• W3130485834 hasPublicationYear "2021" @default.
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• W3130485834 hasAuthorship W3130485834A5011491497 @default.
• W3130485834 hasAuthorship W3130485834A5014510120 @default.

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