Interactions between the promoter and first intron are involved in transcriptional control of alpha 1(I) collagen gene expression.
AUTOR(ES)
Bornstein, P
RESUMO
The first intron of the human collagen alpha 1(I) gene contains several positively and negatively acting elements. We have studied the transcription of collagen-human growth hormone fusion genes, containing deletions and rearrangements of collagen intronic sequences, by transient transfection of chick tendon fibroblasts and NIH 3T3 cells. In chick tendon fibroblasts, but not in 3T3 cells, inversion of intronic sequences containing a previously studied 274-base-pair segment, A274, resulted in markedly reduced human growth hormone mRNA levels as determined by an RNase protection assay. This inhibitory effect was largely alleviated when deletions were introduced in the collagen promoter of plasmids containing negatively oriented intronic sequences. Evidence for interaction of the promoter with the intronic segment, A274, was obtained by gel mobility shift assays. We suggest that promoter-intron interactions, mediated by DNA-binding proteins, regulate collagen gene transcription. Inversion of intronic segments containing critical interactive elements might then lead to an altered geometry and reduced activity of a transcriptional complex in those cells with sufficiently high levels of appropriate transcription factors. We further suggest that the deleted promoter segment plays a key role in directing DNA interactions involved in transcriptional control.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=365578Documentos Relacionados
- Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene.
- Analysis of the collagen alpha 1(I) promoter.
- A highly conserved intronic sequence is involved in transcriptional regulation of the alpha 1(I) collagen gene.
- Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice.
- Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression.