TAILIEUCHUNG - Báo cáo khoa học: Evaluation of potential regulatory elements identi®ed as DNase I hypersensitive sites in the CFTR gene

The cystic ®brosis 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 forCFTRis the mapping of DNase I hypersensitive sites (DHS) within the locus. We previously identi®ed at least 12 clusters of DHS across theCFTRgene andhere further evaluateDHS in introns 2, 3, 10, 16, 17a, 18, 20 and 21 to assess their functional importance in regulation ofCFTRgene expression. . | Eur. J. Biochem. 269 553-559 2002 FEBS 2002 Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene Marios Phvlactides1 Rebecca Rowntree1 Huah Nuthall1 David Usserv2. Ann Wheeler1 and Ann Harris1 1Paediatric Molecular Genetics Institute of Molecular Medicine Oxford University John Radcliffe Hospital UK 2Center for Biological Sequence Analysis Biocentrum DTU Technical University of Denmark Lyngby Denmark 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. Keywords CFTR regulation DNase I hypersensitive sites. The cystic fibrosis transmembrane conductance regulator CFTR gene shows a tightly regulated pattern of temporal and spatial expression though the elements responsible for this remain poorly .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Structural biochemistry
• oxidation
• bacteria
• medical knowledge
• medical research
• analysis of cytoplasmic
• Crystal structure
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine