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- W2293313791 abstract "A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation of CFTR is responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations. CFTR is a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at the CFTR locus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of the CFTR locus in expressing and non-expressing human primary cells, we identified several new contact points between the CFTR promoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increase CFTR expression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin looping via CTCF." @default.
- W2293313791 created "2016-06-24" @default.
- W2293313791 creator A5003310948 @default.
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- W2293313791 creator A5058238476 @default.
- W2293313791 creator A5066521398 @default.
- W2293313791 creator A5079999358 @default.
- W2293313791 date "2015-11-28" @default.
- W2293313791 modified "2023-10-18" @default.
- W2293313791 title "Analysis of long-range interactions in primary human cells identifies cooperativeCFTRregulatory elements" @default.
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- W2293313791 doi "https://doi.org/10.1093/nar/gkv1300" @default.
- W2293313791 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4824072" @default.
- W2293313791 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26615198" @default.
- W2293313791 hasPublicationYear "2015" @default.
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