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Here we address the impact of genomic spacing on these enhancer:promoter interactions and on\n                    <jats:italic>CFTR<\/jats:italic>\n                    gene expression. Using CRISPR\/Cas9, we generated clonal cell lines with deletions between the \u221235\u2009kb airway enhancer and the\n                    <jats:italic>CFTR<\/jats:italic>\n                    promoter in the 16HBE14o\n                    <jats:sup>\u2212<\/jats:sup>\n                    airway cell line, or between the intron 1 (185\u2009+\u200910\u2009kb) intestinal enhancer and the promoter in the Caco2 intestinal cell line. The effect of these deletions on\n                    <jats:italic>CFTR<\/jats:italic>\n                    transcript abundance, as well as the 3D looping structure of the locus was investigated in triplicate clones of each modification. Our results indicate that both small and larger deletions upstream of the promoter can perturb\n                    <jats:italic>CFTR<\/jats:italic>\n                    expression and \u221235\u2009kb enhancer:promoter interactions in the airway cells, though the larger deletions are more impactful. In contrast, the small intronic deletions have no effect on\n                    <jats:italic>CFTR<\/jats:italic>\n                    expression and intron 1 enhancer:promoter interactions in the intestinal cells, whereas larger deletions do. Clonal variation following a specific\n                    <jats:italic>CFTR<\/jats:italic>\n                    modification is a confounding factor particularly in 16HBE14o\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.18142","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T09:09:30Z","timestamp":1708333770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The impact of genomic distance on enhancer\u2010promoter interactions at the\n                    <i>CFTR<\/i>\n                    locus"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-2543","authenticated-orcid":false,"given":"Jenny L.","family":"Kerschner","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University  Cleveland Ohio 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