Document Detail


Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene.
MedLine Citation:
PMID:  11856314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cystic fibrosis transmembrane conductance regulator (CFTR) gene shows a complex pattern of expression, with temporal and spatial regulation that is not accounted for by elements in the promoter. One approach to identifying the regulatory elements for CFTR is the mapping of DNase I hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2, 3, 10, 16, 17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhan- cer/reporter constructs containing the DHS regions showed that those in introns 20 and 21 augmented the activity of the CFTR promoter. Structural analysis of the DNA sequence at the DHS suggested that only the one intron 21 might be caused by inherent DNA structures. Cell specificity of the DHS suggested a role for the DHS in introns 2 and 18 in CFTR expression in some pancreatic duct cells. Finally, regulatory elements at the DHS in introns 10 and 18 may contribute to upregulation of CFTR gene transcription by forskolin and mitomycin C, respectively. These data support a model of regulation of expression of the CFTR gene in which multiple elements contribute to tightly co-ordinated expression in vivo.
Authors:
Marios Phylactides; Rebecca Rowntree; Hugh Nuthall; David Ussery; Ann Wheeler; Ann Harris
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  269     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-02-21     Completed Date:  2002-03-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  553-9     Citation Subset:  IM    
Affiliation:
Paediatric Molecular Genetics, Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, UK.
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MeSH Terms
Descriptor/Qualifier:
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Deoxyribonuclease I / metabolism*
Evaluation Studies as Topic
Humans
Regulatory Sequences, Nucleic Acid*
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/CFTR protein, human; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; EC 3.1.21.1/Deoxyribonuclease I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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