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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2001-1-26
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pubmed:abstractText |
The cystic fibrosis transmembrane conductance regulator gene (CFTR) shows a tightly regulated pattern of expression with spatial and temporal control. The regulatory elements achieving this appear to lie outside the basal promoter of the gene. We previously identified DNase I hypersensitive sites (DHSs) at -79.5 kb and -20.5 kb with respect to the CFTR translational start site which may contain important regulatory elements. We have now investigated further the DHS at -20.5 kb to evaluate its potential function in the regulation of CFTR expression. Finer mapping revealed that the DHS lies at -20.9 kb. Deletion of the DHS from a 310-kb yeast artificial chromosome (YAC) containing the human CFTR gene has shown that this site may be responsible for about 60% of wild-type levels of transcription from the YAC transgene when expressed in Caco2 cells. DNase I footprinting showed several regions of protection within the -20.9 kb region with nuclear extracts from Caco2 cells, but not with extracts from lymphoblastoid cells, which do not show the DHS. Matches to several transcription factor-binding sites were found, but supershift analysis with specific antibodies did not identify the transcription factors involved. Two purine/pyrimidine mirror repeat elements within the -20.9-kb DHS were shown not to adopt non-B-DNA conformations. Thus, we provide evidence for a role for the -20.9 kb DHS in the transcriptional regulation of the CFTR gene, although the mechanisms mediating this effect remain unclear.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CFTR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Superhelical,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Single-Strand Specific DNA and RNA...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0014-2956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
266
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
431-43
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:10561583-Amino Acid Motifs,
pubmed-meshheading:10561583-Base Sequence,
pubmed-meshheading:10561583-Binding Sites,
pubmed-meshheading:10561583-Chromosomes, Artificial, Yeast,
pubmed-meshheading:10561583-Cloning, Molecular,
pubmed-meshheading:10561583-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:10561583-DNA, Superhelical,
pubmed-meshheading:10561583-Deoxyribonuclease I,
pubmed-meshheading:10561583-Electrophoresis, Agar Gel,
pubmed-meshheading:10561583-Exons,
pubmed-meshheading:10561583-Gene Deletion,
pubmed-meshheading:10561583-Gene Expression Regulation,
pubmed-meshheading:10561583-Humans,
pubmed-meshheading:10561583-Models, Genetic,
pubmed-meshheading:10561583-Molecular Sequence Data,
pubmed-meshheading:10561583-Nucleic Acid Conformation,
pubmed-meshheading:10561583-Plasmids,
pubmed-meshheading:10561583-Protein Biosynthesis,
pubmed-meshheading:10561583-Purines,
pubmed-meshheading:10561583-Pyrimidines,
pubmed-meshheading:10561583-RNA, Messenger,
pubmed-meshheading:10561583-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10561583-Sequence Analysis, DNA,
pubmed-meshheading:10561583-Sequence Homology, Nucleic Acid,
pubmed-meshheading:10561583-Single-Strand Specific DNA and RNA Endonucleases,
pubmed-meshheading:10561583-Transcription, Genetic,
pubmed-meshheading:10561583-Transgenes,
pubmed-meshheading:10561583-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Analysis of a DNase I hypersensitive site located -20.9 kb upstream of the CFTR gene.
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pubmed:affiliation |
Paediatric Molecular Genetics, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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