Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of the hepatoma cell line, Hep3B, with gamma-interferon (IFN) enhanced expression of C1 inhibitor (C1INH) mRNA, primarily due to an enhanced transcription rate. Hep3B cells transfected with reporter constructs containing various regions of the C1INH gene between positions -1182 and +587, and stimulated with gamma-IFN, expressed increased levels of chloramphenicol acetyltransferase in the presence of the first intron and as few as 12 bases of the 5'-flanking region. However, a 66% reduction in the inducibility of the constructs was observed when the upstream region between -582 and -252 was eliminated. Successive deletions mapped the first intron IFN-responsive elements to a region between +368 and +410. The data indicate that both the upstream and the first intron sequences can independently enhance induction of C1INH gene expression. Examination of the immediate upstream sequence of the C1INH gene reveals the absence of a TATA box. The promoter of the C1INH gene was mapped to a region within 81 bases of the upstream sequence and the first exon. Further examination indicated two regions that were potentially important for promoter activity as follows: 1) a G-C-rich region from -81 to -49, and 2) an initiator element at -3 to +5. The results indicate that the upstream sequences including -81 to -49 and the H-DNA region between -48 and -17 are not necessary for promotor activity. The initiator element from -3 to +5 is sufficient and necessary for promoter function.
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PMID:Transcriptional regulation of the C1 inhibitor gene by gamma-interferon. 814 55

Mutations disrupting the function or production of C1 inhibitor cause the disease hereditary angioneurotic edema. Patient mutations identified an imperfect inverted repeat sequence that was postulated to play a mechanistic role in the mutations. To test this hypothesis, the inverted repeat was cloned into the chloramphenicol acetyltransferase gene in pBR325 and its mutation rate was studied in four bacterial strains. These strains were selected to assay the effects of recombination and superhelical tension on mutation frequency. Mutations that revert bacteria to chloramphenicol resistance (Cmr) were scored. Both pairs of isogenic strains had reversion frequencies of approximately 10(-8). These rare reversion events in bacteria were most often a frameshift that involved the imperfect inverted repeat with a deletion or a tandem duplication, an event very similar to the human mutations. Increased DNA superhelical tension, which would be expected to enhance cruciform extrusion, did not accentuate mutagenesis. This finding suggests that the imperfect inverted repeat may form a stem-loop structure in the single-stranded DNA created by the duplex DNA melting prior to replication. Models explaining the slippage can be drawn using the lagging strand of the replication fork. In this model, the formation of a stem-loop structure is responsible for bringing the end of the deletion or duplication into close proximity.
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PMID:C1 inhibitor gene sequence facilitates frameshift mutations. 999 Aug 65