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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-5
pubmed:dateCreated
2005-7-22
pubmed:abstractText
Transcriptional regulation of the human alpha 2(I) procollagen proximal promoter involves the interaction of trans-acting factors at the inverted CCAAT box (G/CBE) located at position -80 and an adjacent GGAGGCCC-box at -70. Both these elements have previously been shown to be essential for activity of the human promoter. This study investigated nucleotide differences at three sites (-74, -72 and -71) between the human and mouse promoters that were sufficient to abolish trans-acting factor binding with the mouse sequence (GGAGACGT). Two distinct DNA-protein interactions were detected on the human -107/+54 promoter fragment while a single interaction was observed at the equivalent mouse promoter. One of these factors is the CCAAT-binding factor (CBF) and it's binding was observed on both the human and mouse promoters. Although the GGAGGCCC DNA-binding element was not detected on the mouse promoter, GGAGGCC-binding proteins were present in mouse nuclear extracts as observed by their interaction with the human promoter. Functional analysis of the human and mouse -343/+54 and -107/+54 promoter regions revealed significant differences between species; the human constructs having higher activity than the mouse. The differences in promoter activity between species may in part be a result of the nucleotide differences in the GGAGGCCC-box. Mutations in this region of the human -107/+54 promoter prevented DNA-protein interaction and lowered promoter activity. These results support the hypothesis that the GGAGGCCC-box in the human alpha 2(1) procollagen promoter has a regulatory function and that there exists a species-specific difference in transcription factor binding and regulation of the gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1521-6543
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
363-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16036621-Amino Acid Motifs, pubmed-meshheading:16036621-Animals, pubmed-meshheading:16036621-Base Sequence, pubmed-meshheading:16036621-Cell Nucleus, pubmed-meshheading:16036621-Cells, Cultured, pubmed-meshheading:16036621-Collagen Type I, pubmed-meshheading:16036621-DNA, pubmed-meshheading:16036621-DNA Methylation, pubmed-meshheading:16036621-Fibroblasts, pubmed-meshheading:16036621-Humans, pubmed-meshheading:16036621-Mice, pubmed-meshheading:16036621-Molecular Sequence Data, pubmed-meshheading:16036621-Mutation, pubmed-meshheading:16036621-Procollagen, pubmed-meshheading:16036621-Promoter Regions, Genetic, pubmed-meshheading:16036621-Protein Binding, pubmed-meshheading:16036621-Species Specificity, pubmed-meshheading:16036621-Transcription, Genetic, pubmed-meshheading:16036621-Transfection
pubmed:articleTitle
Species-specific regulation of the alpha-2(I) procollagen gene by proximal promoter elements.
pubmed:affiliation
Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't