Analysis of DNase-I-hypersensitive sites at the 3' end of the cystic fibrosis transmembrane conductance regulator gene (CFTR)

Hugh N. Nuthall, Danielle S. Moulin, Clare Huxley, Ann Harris*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The cystic fibrosis transmembrane conductance regulator gene (CFTR) exhibits a complex pattern of expression that shows temporal and spatial regulation, although the control mechanisms are not fully known. We have mapped DNase-I-hypersensitive sites (DHSs) flanking the CFTR gene with the aim of identifying potential regulatory elements. We previously characterized DHSs at -79.5 and -20.9 kb with respect to the CFTR translational start site and a regulatory element in the first intron of the gene at 185 + 10 kb. We have now mapped five DHSs lying 3' to the CFTR gene at 4574 + 5.4, +6.8, +7.0, +7.4 and +15.6 kb that show some degree of tissue specificity. The DHSs are seen in chromatin extracted from human primary epithelial cells and cell lines; the presence of the +15.6 kb site is tissue-specific in transgenic mice carrying a human CFTR yeast artificial chromosome. Further analysis of the 4574 + 15.6 kb DHS implicates the involvement of CCAAT-enhancer-binding protein (C/EBP), cAMP-response-element-binding protein (CREB)/activating transcription factor (ATF) and activator protein 1 (AP-1) family transcription factors at this regulatory element.

Original languageEnglish (US)
Pages (from-to)601-611
Number of pages11
JournalBiochemical Journal
Volume341
Issue number3
DOIs
StatePublished - Aug 1 1999

Keywords

  • DHS
  • Regulation of expression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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