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 distal promoter of Adh is differentially expressed in Drosophila tissue culture cell lines. After transfection with an exogenous Adh gene, there was a specific increase in distal alcohol dehydrogenase (ADH) transcripts in ADH-expressing (ADH+) cells above the levels observed in transfected ADH-nonexpressing (ADH-) cells. We used deletion mutations and a comparative transient-expression assay to identify the cis-acting elements responsible for enhanced Adh distal transcription in ADH+ cells. DNA sequences controlling high levels of distal transcription were localized to a 15-base-pair (bp) region nearly 500 bp upstream of the distal RNA start site. In addition, a 61-bp negative cis-acting element was found upstream from and adjacent to the enhancer. When this silencer element was deleted, distal transcription increased only in the ADH+ cell line. These distant upstream elements must interact with the promoter elements, the Adf-1-binding site and the TATA box, as they only influenced transcription when at least one of these two positive distal promoter elements was present. Internal deletions targeted to the Adf-1-binding site or the TATA box reduced transcription in both cell types but did not affect the transcription initiation site. Distal transcription in transfected ADH- cells appears to be controlled primarily through these promoter elements and does not involve the upstream regulatory elements. Evolutionary conservation in distantly related Drosophila species suggests the importance of these upstream elements in correct developmental and tissue-specific expression of ADH.
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PMID:Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines. 169 13

A transient expression assay has been used to investigate the cause of a tissue-specific position effect on Adh expression from a transgene insertion in Drosophila. A 15.4-kb genomic clone containing the 3.2-kb Adh insert along with flanking regions of genomic DNA is expressed in this assay in a tissue-specific pattern resembling the abnormal expression pattern of the position effect. The 3.2-kb Adh insert is expressed normally without the flanking sequences. A silencer element is located upstream of the Adh gene within a 2-kb fragment that acts in both orientations and at a distance of at least 6.5 kb from the larval Adh promoter to suppress ADH expression in a nontissue specific fashion. The DNA sequence of the 2-kb fragment indicates that it is a noncoding region. A 17-bp sequence is repeated within this region and may be associated with the silencer activity, since subclones from the 2-kb fragment, each containing one of the repeated regions, both retain full silencer activity. This silencer fails to suppress expression from an alpha 1-tubulin promoter-LacZ fusion construct or an hsp70 promoter-Adh fusion construct. In addition to the silencer, another element is located downstream of the Adh gene that produces a higher level of anterior than posterior midgut expression. These results suggest that the 5' silencer and the 3' element act together to create the tissue specific position effect characteristic of the GC-1 line.
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PMID:Isolation of silencer-containing sequences causing a tissue-specific position effect on alcohol dehydrogenase expression in Drosophila melanogaster. 820 25

The molecular basis for the abnormal expression of an alcohol dehydrogenase (Adh) transgene, introduced into the 25 C-D region of an Adh negative strain of Drosophila melanogaster, was investigated using a transient expression assay. A 14-kb genomic clone from the transformed line, MM-50, containing the transgene was isolated. A position effect element was identified upstream of the Adh gene within a 1.7-kb EcoRI fragment. This element acts as a silencer, greatly reducing the Adh transcriptional activity. Sequence analysis reveals that the silencer element is 1.18 kb long. There are no long open reading frames present in the sequence, suggesting that it is derived from a noncoding region. A 20-bp sequence (17/20 nucleotides matching) containing a high T/C content is repeated within the silencer region. Within each of these homologous regions there is an internal repeat of the sequence CTCTC. The repeated sequences in MM-50 contain a consensus motif, CCTCTC, for silencer elements found in the rat collagen II gene and several other vertebrate genes, including the human beta-interferon (beta-IFN) gene. Comparison of the sequence of the silencer region to the D. melanogaster whole genome sequence shows that the silencer is located within a clone derived from the 25C5-25C10 region of chromosome 2L.
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PMID:Localization of a position effect element that affects alcohol dehydrogenase transgene expression in Drosophila melanogaster. 1216 8