Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human ADH1, ADH2, and ADH3 genes are closely related members of a gene family which are differentially expressed during liver development. To begin examining the mechanism of this tissue-specific and stage-specific expression, the 5'-flanking nucleotide (nt) sequences of the three genes were determined and the transcription start point (tsp) were identified. Sequences of all three genes indicated a high degree of homology (greater than 80% nt sequence identity) from the AUG translation start codon to about nt -780 relative to the tsp. Transient transfection assays of a set of plasmids containing various lengths of ADH 5'-flanking DNA fused to cat were performed in the HepG2 and Hep3B human hepatoma cell lines. The results indicated that the ADH2 promoter-proximal region was transcriptionally active in the absence of upstream sequences. To identify potential cis-acting elements in the ADH2 promoter-proximal region, a DNase I footprinting assay using a rat liver nuclear extract was used. Protection occurred in several locations including one, between nt -51 and -10, which shares homology with known binding sites for a previously identified rat-liver transcription factor called CCAAT/enhancer binding protein (C/EBP). Purified C/EBP was shown by footprint analysis to bind at two distinct sites in the ADH2 promoter located at nt -51 to -31 and -21 to -10. The TATA-box promoter element at nt -30 to -22 was not protected by C/EBP, but was partially protected by a factor in the rat liver nuclear extract. Thus, it is possible that the flanking C/EBP molecules may create a novel binding pocket for TFIID, the TATA-binding general transcription factor for RNA polymerase II. Alternatively, the C/EBP molecules may block access to the TATA box, and stimulate transcription of ADH2 by interacting with some component(s) other than TFIID.
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PMID:Promoters for the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3: interaction of CCAAT/enhancer-binding protein with elements flanking the ADH2 TATA box. 216 44

Analysis of puffing patterns in Drosophila melanogaster salivary gland chromosomes indicates the existence of a developmentally specific puff in the 35B region. This puff seems to originate from bands 35B2 or 35B3, where Adh is located, and it is expanded in more than 60% of the nuclei examined. The presence of RNA polymerase II in this puff as well as its ability to incorporate tritiated uridine shows that it corresponds to a transcriptionally active site. RNA blotting and in situ hybridization experiments indicate that Adh is transcribed, although not very actively, in salivary glands during the third larval instar. However, this tissue does not display detectable levels of ADH activity. By contrast, we have found that in midgut polytene chromosomes the 35B region is not visibly puffed in spite of the high levels of Adh transcripts detected. These results seem to suggest that puffing at the 35B region could be mainly promoted by genes closely linked to Adh, possibly with a minor contribution of this gene.
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PMID:A cytological and molecular analysis of Adh gene expression in Drosophila melanogaster polytene chromosomes. 246 76

Promoters were isolated at random from the genome of Saccharomyces cerevisiae by using a plasmid that contains a divergently arrayed pair of promoterless reporter genes. A comprehensive library was constructed by inserting random (DNase I-generated) fragments into the intergenic region upstream from the reporter genes. Simple in vivo assays for either reporter gene product (alcohol dehydrogenase or beta-galactosidase) allowed the rapid identification of promoters from among these random fragments. Poly(dA-dT) homopolymer tracts were present in three of five randomly cloned promoters. With two exceptions, each RNA start site detected was 40 to 100 base pairs downstream from a TATA element. All of the randomly cloned promoters were capable of activating reporter gene transcription bidirectionally. Interestingly, one of the promoter fragments originated in a region of the S. cerevisiae rDNA spacer; regulated divergent transcription (presumably by RNA polymerase II) initiated in the same region.
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PMID:Properties of promoters cloned randomly from the Saccharomyces cerevisiae genome. 284 31

A 569-base pair fragment encompassing the upstream regulatory region, the RNA initiation sites, and the initial part of the coding region of the Saccharomyces cerevisiae alcohol dehydrogenase II gene has been analyzed for the presence of sites which undergo conformational modification under torsional stress. Fine mapping of P1 and S1 endonuclease-sensitive sites was obtained on single topoisomers produced by in vitro ligation. It was shown that the upstream activator sequence, the TATA sequence, a region directly upstream to the RNA initiation sites, and several positions in the first segment of the transcribed region change conformation as a function of the applied torsional stress in a precisely coordinate fashion. The superhelical density optima for this coordinate modifications have been determined. Analysis of the conformational changes of the promoter sequence in several naturally occurring (Young, E. T., Williamson, V. M., Taguchi, A., Smith, M., Sledziewski, L., Russel, D., Osterman, J., Denis, C., Cox, D., and Beier, D., (1982) in Genetic Engineering of Microorganisms for Chemicals (Hollander, A., De Moss, R. D., Kaplan, S., Konisky, J., Savage, D., and Wolle, R. S., eds) pp. 335-361, Plenum Publishing Corp., New York) up-promoter constitutive mutants was performed. This analysis has shown that the conformation of functionally relevant sites changes as a function of sequence mutations that have taken place elsewhere; this shows that the conformational behavior of the whole promoter region is linked and suggests transmission in cis of topological effects in RNA polymerase II promoters.
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PMID:The intrinsic topological information of the wild-type and of up-promoter mutations of the Saccharomyces cerevisiae alcohol dehydrogenase II regulatory region. 305 83

The fission yeast Schizosaccharomyces pombe has proved an important model system for cross-species comparative studies of many fundamental processes in the eukaryotic cell, such as cell cycle control and DNA replication. The RNA polymerase II transcription machinery is, however, still relatively poorly understood in S. pombe, partially due to the absence of a reconstituted in vitro transcription system. We have now purified S. pombe RNA polymerase II and its general initiation factors TFIIB, TFIIF, TFIIE, and TFIIH to near homogeneity. These factors enable RNA polymerase II to initiate transcription from the S. pombe alcohol dehydrogenase promoter (adh1p) when combined with Saccharomyces cerevisiae TATA-binding protein. We use our reconstituted system to examine effects of Mediator on basal transcription in vitro. S. pombe Mediator exists in two distinct forms, a free form, which contains the spSrb8, spTrap240, spSrb10, and spSrb11 subunits, and a smaller form, which lacks these four subunits and associates with RNA polymerase II to form a holoenzyme. We find that spSrb8/spTrap240/spSrb10/spSrb11 containing Mediator repress basal transcription, whereas Mediator lacking these subunits has a stimulatory effect on transcription. Our findings thus demonstrate that the spSrb8/spTrap240/spSrb10/spSrb11 subcomplex governs the ability of Mediator to stimulate or repress basal transcription in vitro.
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PMID:Mediator influences Schizosaccharomyces pombe RNA polymerase II-dependent transcription in vitro. 1453 14