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• W2923621500 endingPage "235" @default.
• W2923621500 startingPage "235" @default.
• W2923621500 abstract "The cystic fibrosis transmembrane conductance regulator (CFTR) gene is an attractive target for gene editing approaches, which may yield novel therapeutic approaches for genetic diseases such as cystic fibrosis (CF). However, for gene editing to be effective, aspects of the three-dimensional (3D) structure and cis-regulatory elements governing the dynamic expression of CFTR need to be considered. In this review, we focus on the higher order chromatin organization required for normal CFTR locus function, together with the complex mechanisms controlling expression of the gene in different cell types impaired by CF pathology. Across all cells, the CFTR locus is organized into an invariant topologically associated domain (TAD) established by the architectural proteins CCCTC-binding factor (CTCF) and cohesin complex. Additional insulator elements within the TAD also recruit these factors. Although the CFTR promoter is required for basal levels of expression, cis-regulatory elements (CREs) in intergenic and intronic regions are crucial for cell-specific and temporal coordination of CFTR transcription. These CREs are recruited to the promoter through chromatin looping mechanisms and enhance cell-type-specific expression. These features of the CFTR locus should be considered when designing gene-editing approaches, since failure to recognize their importance may disrupt gene expression and reduce the efficacy of therapies." @default.
• W2923621500 created "2019-04-01" @default.
• W2923621500 creator A5010913875 @default.
• W2923621500 creator A5085606046 @default.
• W2923621500 date "2019-03-19" @default.
• W2923621500 modified "2023-09-25" @default.
• W2923621500 title "Cell-Selective Regulation of CFTR Gene Expression: Relevance to Gene Editing Therapeutics" @default.
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