Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct.
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PMID:Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos. 190 38

The B lymphoblastoid cell line clone 13 (a subclone of the mutant cell line P3JHR-1) has been found to express high levels of HLA-DQ; by contrast, HLA-DR and -DP antigens are not expressed and cannot be induced by interferon gamma. Northern blot analysis using gene-specific probes indicated that the lack of surface expression of the DR and DP antigens is due to a marked decrease in the levels of steady-state RNA for both the alpha and beta chains. Southern blots demonstrated that none of the transcriptionally repressed genes are grossly deleted. Preparations of interspecific transient heterokaryons between clone 13 and the class II antigen-positive murine B cell lymphoma, A20, resulted in reactivation of the DRA gene and surface expression of both the DR and DP molecules. The efficiency of the DRA promoter relative to the DQB promoter is markedly and specifically diminished in clone 13 (P3JHR-1) as compared with the parental cell line, Jijoye, as assayed both by transient expression of appropriate chloramphenicol acetyltransferase gene (CAT) constructs and by in vitro transcription analysis. These data clearly demonstrate the existence of an isotype-specific trans-acting factor, and provide direct evidence that the highly homologous class II genes have distinct regulatory mechanisms.
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PMID:An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP. 199 50

We mapped cis-acting regulatory elements in the HLA-DR alpha gene, which encodes the monomorphic subunit of the HLA-DR heterodimer. Genomic fragments of HLA-DR alpha were placed 5' or 3' to the chloramphenicol acetyltransferase reporter gene, the transcription of which was initiated from the Herpes simplex thymidine kinase promoter. In transient expression assays, fragments from the body of the HLA-DR alpha gene were able to increase chloramphenicol acetyltransferase activity in a position-, orientation-, and promoter-independent yet tissue-specific fashion. These HLA-DR alpha cis-acting regulatory elements contain previously identified DNase I-hypersensitive sites and DNA sequences homologous to those found in other eukaryotic transcriptional enhancers.
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PMID:A tissue-specific transcriptional enhancer is found in the body of the HLA-DR alpha gene. 347 84

The regulation of HLA class II genes is of particular interest with regard to the modulation of the immune response. The polymorphism of their coding regions is directly involved in the specificity of the Ag presentation, and their level of expression affects the extent of T cell activation. Previously, we have described an allelic polymorphism in the proximal promoter regions of HLA-DRB genes. The aim of this study was to compare the transcriptional activities of the promoters of the DRB genes and DRB1 alleles in a transient expression system. We have demonstrated a marked difference in their promoter strengths, as determined by their relative abilities to initiate transcription of the chloramphenicol acetyltransferase reporter gene in human B cell lines. The polymorphism of the promoter regions has been mapped to the regulatory boxes, and, by using gel retardation experiments, we found a differential ability of the nuclear proteins to bind to the partially conserved X box regions. Taken together, our results demonstrate the functional consequences of the allelic polymorphism of the proximal promoter regions of the DRB genes. These findings strongly suggest the existence, for the HLA-DR genes, of an interdependence between the polymorphism of the coding regions, which directly affects the capacity of peptide binding, and the polymorphism of the regulatory regions, which influences the transcriptional activities of the promoters.
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PMID:Differential transcriptional activities of HLA-DR genes in the various haplotypes. 796 65

In previous studies we reported that the expression of HLA-DR on melanoma cell lines was differentially modulated by IFN- gamma and that the transcription rate was responsible for this differential modulation. We have also reported the nucleotide sequence variations in the promoter region of HLA-DR genes, and proposed that differences in the promoter activity by the sequence variations of the HLA-DR promoters might contribute to such a differential transcriptional regulation at the promoter level. In this study, in order to assess whether the sequence variations of the HLA-DR promoters affect the factor binding and exert influence on the promoter activity, nuclear factor binding to our previous six HLA-DRA and fourteen HLA-DRB promoter clones was evaluated with the nuclear protein extracted from a B-lymphoblastoid cell line (BLCL), BH, together with the chloramphenicol acetyltransferase (CAT) reporter assay. In the HLA-DRA promoters, clone #35 containing one bp nucleotide sequence variation at the octamer binding site (OCT) (GATTTGC to GATCTGC) showed relatively weak factor binding. In the HLA-DRB promoters, clusters I, III, and IV of our previous HLA-DRB promoter homologues, containing one bp nucleotide sequence variation (GATTCG) in their Y boxes exhibited weak factor binding and CAT activity compared to other clusters (GATTGG) that showed strong factor binding and CAT activity. This data suggests chat the binding patterns of transcription factors influenced by the nucleotide sequence variations of the HLA-DR promoter could affect the promoter activity and the DNA sequence elements in the HLA-DR promoter could mediate transcriptional regulation.
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PMID:Influence of the sequence variations of the HLA-DR promoters derived from human melanoma cell lines on nuclear protein binding and promoter activity. 1107 19

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