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dc.contributor.authorBlackledge, NPen_US
dc.contributor.authorCarter, EJen_US
dc.contributor.authorEvans, JRen_US
dc.contributor.authorLawson, Ven_US
dc.contributor.authorRowntree, RKen_US
dc.contributor.authorHarris, Aen_US
dc.identifier.citationBIOCHEMICAL JOURNAL, 2007, 408 pp. 267 - 275en_US
dc.description.abstractRegulatory elements that lie outside the basal promoter of a gene may be revealed by local changes in chromatin structure and histone modifications. The promoter of the CFTR (cystic fibrosis transmembrane conductance regulator) gene is not responsible for its complex pattern of expression. To identify important regulatory elements for CFTR we have previously mapped DHS (DNase I-hypersensitive sites) across 400 kb spanning the locus. Of particular interest were two DHS that flank the CFTR gene, upstream at -20.9 kb with respect to the translational start site, and downstream at + 15.6 kb. In the present study we show that these two DHS possess enhancer-blocking activity and bind proteins that are characteristic of known insulator elements. The DHS core at - 20.9 kb binds CTCF (CCCTC-binding factor) both in vitro and in vivo; however, the + 15.6 kb core appears to bind other factors. Histone-modification analysis across the CFTR locus highlights structural differences between the - 20.9 kb and + 15.6 kb DHS, further suggesting that these two insulator elements may operate by distinct mechanisms. We propose that these two DHS mark the boundaries of the CFTR gene functional unit and establish a chromatin domain within which the complex profile of CFTR expression is maintained.en_US
dc.format.extent267 - 275en_US
dc.titleCTCF mediates insulator function at the CFTR locusen_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBIOCHEMICAL JOURNALen_US
pubs.notesaffiliation: Harris, A (Reprint Author), Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, 2300 Childrens Plaza 211, Chicago, IL 60614 USA. Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Chicago, IL 60614 USA. Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England. Inst Canc Res, London SW3 6JB, England. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. keywords: CCCTC-binding factor (CTCF); chromatin structure; cystic fibrosis transmembrane conductance regulator (CFTR); DNase I-hypersensitive site; histone modification; insulator keywords-plus: RETINOID-X-RECEPTOR; I-HYPERSENSITIVE SITES; POTENTIAL REGULATORY ELEMENTS; TRANSCRIPTION FACTOR-BINDING; ENHANCER-BLOCKING ACTIVITY; THYROID-HORMONE RECEPTOR; BETA-GLOBIN INSULATOR; CYSTIC-FIBROSIS; GENE-EXPRESSION; PROTEIN CTCF research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology author-email: number-of-cited-references: 53 times-cited: 28 usage-count-last-180-days: 0 usage-count-since-2013: 2 journal-iso: Biochem. J. doc-delivery-number: 239CU unique-id: ISI:000251496900013 oa: gold_or_bronze da: 2018-08-30en_US
pubs.notesNot knownen_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorLawson, Victoriaen_US

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