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)

By comparing the upstream DNA sequence of the rat and human genes encoding poly(ADP-ribose) polymerase (PARP), we have defined a 16-bp conserved region and designated it as US-1 for 'upstream sequence 1'. This element is homologous to the recently described binding site for the transcription factor Sp1 in the promoter sequence of the mouse p12 gene which encodes a protease inhibitor. Analyses in gel mobility shift assays revealed that a nuclear protein, produced by all tissue-culture cells tested, specifically binds the US-1 element. The pattern of shifted DNA protein complexes obtained was strikingly similar to that for Sp1, which is supported by the positive displacement of these complexes by an oligomer containing the Sp1 binding site in gel shift competition experiments. Replacement of the Sp1 binding site from the basal promoter of the mouse p12 gene by the rPARP US-1 element did not result in any significant variations in the level of expression of the chloramphenicol acetyltransferase (CAT) reporter gene upon transient transfection of tissue-culture cells. However, when point mutations are introduced in the US-1 element in a similar substitution experiment, a significant reduction in CAT gene expression could be observed. These data are consistent with Sp1 interacting with the US1 element. Results from DNase I footprinting experiments clearly indicated that purified Sp1 not only binds to the US-1 element but also to four other closely located cis-acting sites scattered in the promoter of the rat PARP gene, therefore suggesting that Sp1 is likely to modulate strongly the expression of that gene in different tissues.
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PMID:The US-1 element from the gene encoding rat poly(ADP-ribose) polymerase binds the transcription factor Sp1. 834 87

High levels of expression for the rat growth hormone (rGH) gene are restricted to the somatotroph cells of the anterior pituitary. Previously, we have shown that rGH cell-specific repression results in part from the recognition of negatively acting silencers by a number of nuclear proteins that repress basal promoter activity. Examination of these silencers revealed the presence of binding sites for proteins that belong to the NF1 family of transcription factors. Indeed, proteins from this family were shown to bind the rGH proximal silencer (designated silencer-1) in in vitro assays. Furthermore, this silencer site is capable of repressing chloramphenicol acetyltransferase (CAT) gene expression driven by an heterologous promoter (that of the mouse p12 gene), even in pituitary cells. Recently, we identified in the 5' untranslated region of the gene encoding human cellular retinol binding protein 1 (hCRBP1) a negative regulatory element (Fp1) that also bears an NF1 binding site very similar to that of rGH silencer-1. However, although deletion of Fp1 in the hCRBP1 gene yielded increased CAT activity, pointing toward a negative regulatory function exerted by this element, its insertion upstream of the p12 basal promoter results in an impressive positive stimulation of CAT gene expression. By exploiting NaDodSO4 gel protein fractionation and renaturation, we identified a 40-kD nuclear protein (designated Bp1) present in GH4C1 cells that binds very strongly to rGH silencer-1 but only weakly to hCRBP1 Fp1. Similarly, we also detected a 29-kD nuclear factor (designated Bp2) that recognizes exclusively the Fp1 element as its target site, therefore suggesting that different, but likely related, proteins bind these homologous elements to either activate or repress gene transcription. Although they bind DNA through the recognition of the NF1-like target sequence contained on these elements, competition and supershift experiments in electrophoretic mobility shift assays provided evidence that neither of these proteins belong to the NF1 family.
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PMID:The rat growth hormone and human cellular retinol binding protein 1 genes share homologous NF1-like binding sites that exert either positive or negative influences on gene expression in vitro. 930 37

DNA polymerase delta consists of at least four subunits: p125, p68, p50, and p12 [Liu et al., J. Biol. Chem. 275 (2000) 18739-18744]. We have isolated genomic DNA clones covering the gene for the human DNA polymerase delta 50 kDa subunit (POLD2) and its 5'-flanking sequence. The POLD2 gene is composed of 11 exons and is distributed over 10 kb of genomic DNA. All exon-intron splice junctions conformed to the GT/AG consensus sequence. The 5'-flanking region of human POLD2 is G+C-rich and does not have a typical TATA box. A computer-based search for potential transcription factor binding sites revealed the existence of a number of motifs including those for AP1, AP2, Sp1, NF-1 and CREB. The functional activity of the regulatory region of the human POLD2 gene was demonstrated by its ability to drive the expression of a chloramphenicol acetyltransferase reporter gene in COS-7 cells.
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PMID:Characterization of the 5'-flanking region of the gene encoding the 50 kDa subunit of human DNA polymerase delta. 1097 29