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)

A truncated mouse alphafetoprotein (AFP) gene promoter/enhancer region was tested for its ability to regulate the expression of the Escherichia coli chloramphenicol acetyltransferase (CAT) reporter gene in the livers of transgenic mice. The AFP regulatory region lacked any AFP gene structural DNA, included one enhancer sequence together with the proximal promoter sequence, and an element believed to be responsible for the postnatal repression of AFP gene transcription. The neonatal livers of AFP/CAT transgenic mice showed a high level of CAT enzyme expression, which was dramatically reduced between 7 and 14 days after birth. The staining of liver sections with anti-CAT antibodies showed that this expression was limited to hepatocytes. In one lineage, reexpression of CAT in the adult liver could be achieved by restitutive proliferation of hepatocytes following partial hepatectomy or CCl4-induced necrosis; reexpression in young animals (3-4 weeks of age) was even greater. These studies show that a truncated AFP promoter/enhancer region functions in a tissue-specific and developmental stage-specific fashion, and may be used to control the expression of other genes in the livers of transgenic mice.
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PMID:Developmental control of transcription of the CAT reporter gene by a truncated mouse alphafetoprotein gene regulatory region in transgenic mice. 856 43

Type I collagen synthesis and deposition is generally indicative of irreversible damage in alcohol-induced cirrhosis in humans. However, in rodents, ethanol alone does not readily cause hepatic fibrosis. To determine whether this is because of a lack of ethanol-responsive elements, an artificial enhancer construct controlling rat type I collagen gene transcription was prepared in transgenic mice. The gene construct, ColCAT3.6, was a chimeric sequence containing the marker chloramphenicol acetyltransferase (CAT) gene linked to 3.5 kb of the rat alpha 1(I) 5'-flanking DNA, and 115 base pairs (bp) of transcribed collagen gene. Groups of transgenic mice were given 4 g/kg ethanol orally, twice daily for 4 weeks. As a positive control for hepatic fibrosis, transgenic mice were given intraperitoneal injections of CCl4, twice weekly for 4 weeks. Livers were assayed for CAT activity. Endogenous mouse collagen alpha 1(I) messenger RNA (mRNA) and transgene CAT mRNA were measured by RNase protection assays. Collagen synthesis in livers from the transgenic mice treated with ethanol were increased over controls, but the levels were not significantly different. Endogenous collagen alpha 1(I) steady-state mRNA levels in ethanol-treated mice were not significantly different compared with saline-treated controls. However, the transgene mRNA levels in ethanol-treated animals increased approximately 21-fold compared with saline-treated controls, as measured by RNase protection assays. Furthermore, the transgene product as measured by CAT activity in ethanol-treated mice was significantly increased threefold over saline-treated controls. We conclude that the 5'-flanking region of the rat alpha 1(I) collagen gene does contain regulatory elements that are strongly responsive to ethanol administration.
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PMID:A collagen enhancer-promoter construct in transgenic mice is markedly stimulated by ethanol administration. 859 57

Recently, we demonstrated that the function of ATF3, a stress-inducible transcriptional repressor, is negatively regulated by a bZip protein, gadd153/Chop10. In this report, we present evidence that ATF3 can repress the expression of its own inhibitor, gadd153/Chop10. First, ATF3 represses a chloramphenicol acetyltransferase reporter gene driven by the gadd153/Chop10 promoter when assayed by a transfection assay in vivo and a transcription assay in vitro. Second, the gadd153/Chop10 promoter contains two functionally important binding sites for ATF3: an AP-1 site and a C/EBP-ATF composite site, a previously unidentified binding site for ATF3. The absence of either site reduces the ability of ATF3 to repress the promoter. Third, overexpression of ATF3 by transient transfection results in a reduction of the endogenous gadd153/Chop10 mRNA level. Fourth, as described previously, ATF3 is induced in the liver upon CCl4 treatment. Intriguingly, we show in this report that gadd153/Chop10 mRNA is not present in areas where ATF3 is induced. Taken together, these results strongly suggest that ATF3 represses the expression of gadd153/Chop10. The mutual negative regulation between ATF3 and gadd153/Chop10 is discussed.
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PMID:gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3. 934 34

Hepatic stellate cells become activated during the early stages of hepatic injury associated with fibrogenesis. The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGFIIR) plays an important role in early fibrogenesis by participating in the activation of latent transforming growth factor-beta, a potent inducer of the matrix proteins in activated stellate cells that define the fibrotic phenotype. In this study we examined hepatic stellate cell regulation of M6P/IGFIIR expression and found that M6P/IGFIIR mRNA transcript levels increased in stellate cells from rats exposed to carbon tetrachloride (CCl4), a potent fibrogenic stimulant. Two E-boxes residing in the proximal promoter of M6P/IGFIIR were found to each bind a novel 75-kDa transcription factor (P75) in quiescent stellate cells of normal livers. This E-box binding was down-regulated as an early response in stellate cells exposed to CCl4, coinciding with increased M6P/IGFIIR transcript levels. Mutagenized E-boxes in M6P/IGFIIR promoter-chloramphenicol acetyltransferase (CAT) reporter constructs produced a substantial increase in reporter expression when compared with the corresponding native promoter-CAT construct when transfected in culture-activated stellate cells, suggesting P75's role as a repressor. The results indicate P75's participation in the regulation of M6P/IGFIIR transcription in hepatic stellate cells during fibrogenesis.
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PMID:E-box-binding repressor is down-regulated in hepatic stellate cells during up-regulation of mannose 6-phosphate/insulin-like growth factor-II receptor expression in early hepatic fibrogenesis. 963 37