Transcriptional repression of the alpha 1(I) collagen gene by ras is mediated in part by an intronic AP1 site.
We have previously shown that transformation of fibroblasts by ras results in transcriptional inhibition of the alpha 1(I) gene. An alpha 1(I)-hGH chimeric plasmid containing 3.7 kb of 5' flanking and 4.4 kb of alpha 1(I) transcribed sequence was regulated appropriately by ras in a transient transfection assay. In contrast, a similar plasmid containing alpha 1(I) DNA from -220 to +500 was virtually unresponsive to ras. The regions from -3700 to -220 and +500 to +4400 contributed equally to the ras-mediated inhibition of the parental plasmid. Deletion analysis indicated that a short fragment, between +500 and +890 in the first intron of the alpha 1(I) gene, was recognized differently in ras-transformed and wild-type cells. A previously described AP1 site in this fragment stimulated alpha 1(I) transcription in Rat1 fibroblasts but was inactive in ras-transformed cells. Mobility shift assays using nuclear extracts from the two cell types demonstrated differences in binding to the alpha 1(I) AP1 site. We conclude that ras transformation suppresses the function of a cell-specific enhancer in the first intron of the alpha 1(I) collagen gene.[1]References
- Transcriptional repression of the alpha 1(I) collagen gene by ras is mediated in part by an intronic AP1 site. Slack, J.L., Parker, M.I., Bornstein, P. J. Cell. Biochem. (1995) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
