| Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene. | |
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MedLine Citation:
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PMID: 11856314 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Marios Phylactides; Rebecca Rowntree; Hugh Nuthall; David Ussery; Ann Wheeler; Ann Harris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 269 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 2002 Jan |
Date Detail:
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Created Date: 2002-02-21 Completed Date: 2002-03-19 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: Germany |
Other Details:
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Languages: eng Pagination: 553-9 Citation Subset: IM |
Affiliation:
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Paediatric Molecular Genetics, Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cystic Fibrosis Transmembrane Conductance Regulator
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genetics* Deoxyribonuclease I / metabolism* Evaluation Studies as Topic Humans Regulatory Sequences, Nucleic Acid* Transfection Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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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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