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Publication : Presence of transcription regulatory elements within an intron of the virus-inducible murine TIMP gene.

First Author  Coulombe B Year  1988
Journal  Mol Cell Biol Volume  8
Issue  8 Pages  3227-34
PubMed ID  2850484 Mgi Jnum  J:20066
Mgi Id  MGI:68179 Doi  10.1128/mcb.8.8.3227
Citation  Coulombe B, et al. (1988) Presence of transcription regulatory elements within an intron of the virus-inducible murine TIMP gene. Mol Cell Biol 8(8):3227-34
abstractText  The expression of the gene for the murine tissue inhibitor of metalloproteinases (TIMP) is induced in response to viruses, growth factors, and phorbol esters. In this report we show that the accumulation of TIMP mRNA after Newcastle disease virus induction is caused by transcriptional activation of the gene. Comparison of the sequences of cDNA and genomic clones along with RNase protection and primer extension analyses revealed that the murine TIMP gene possesses multiple cap sites and that the exon 1 consists exclusively of 5'-noncoding sequences. We observed that DNA regions analogous to those found upstream of the virus-inducible interferon genes are present within intron 1 of the TIMP gene. To investigate the possible role of TIMP intron 1 in gene expression, we used a functional assay based on the transfection of plasmids in which the DNA segment to be tested is placed in proximity to a marker gene driven by the heterologous herpes simplex virus thymidine kinase promoter. Our results indicate that TIMP intron 1 contains DNA sequence elements capable of modulating the activity of a heterologous promoter in two different ways: (i) by enhancing constitutive expression and (ii) by conferring virus inducibility. These results suggest that intron 1 may be involved in the transcriptional regulation of TIMP gene expression.
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