scholarly journals Pleiotropic Effect of Disrupting a Conserved Sequence Involved in a Long-Range Compensatory Interaction in the Drosophila Adh Gene

Genetics ◽  
2004 ◽  
Vol 166 (1) ◽  
pp. 237-242 ◽  
Author(s):  
John F. Baines ◽  
John Parsch ◽  
Wolfgang Stephan
Keyword(s):  
Long Range ◽  
Pleiotropic Effect ◽  
Conserved Sequence ◽  
Adh Gene ◽  
Drosophila Adh

scholarly journals A Highly Conserved Sequence in the 3′-Untranslated Region of the Drosophila Adh Gene Plays a Functional Role in Adh Expression

Genetics ◽  
1999 ◽  
Vol 151 (2) ◽  
pp. 667-674 ◽  
Author(s):  
John Parsch ◽  
Wolfgang Stephan ◽  
Soichi Tanda
Keyword(s):  
Amino Acid ◽  
Untranslated Region ◽  
Functional Role ◽  
P Element ◽  
Evolutionary Significance ◽  
Base Sequence ◽  
Twofold Increase ◽  
Conserved Sequence ◽  
Adh Gene ◽  
Adh Activity

Abstract Phylogenetic analysis identified a highly conserved eight-base sequence (AAGGCTGA) within the 3′-untranslated region (UTR) of the Drosophila alcohol dehydrogenase gene, Adh. To examine the functional significance of this conserved motif, we performed in vitro deletion mutagenesis on the D. melanogaster Adh gene followed by P-element-mediated germline transformation. Deletion of all or part of the eight-base sequence leads to a twofold increase in in vivo ADH enzymatic activity. The increase in activity is temporally and spatially general and is the result of an underlying increase in Adh transcript. These results indicate that the conserved 3′-UTR motif plays a functional role in the negative regulation of Adh gene expression. The evolutionary significance of our results may be understood in the context of the amino acid change that produces the ADH-F allele and also leads to a twofold increase in ADH activity. While there is compelling evidence that the amino acid replacement has been a target of positive selection, the conservation of the 3′-UTR sequence suggests that it is under strong purifying selection. The selective difference between these two sequence changes, which have similar effects on ADH activity, may be explained by different metabolic costs associated with the increase in activity.

scholarly journals Alterations to the remote control of Shh gene expression cause congenital abnormalities

2013 ◽  
Vol 368 (1620) ◽  
pp. 20120357 ◽  
Author(s):  
Robert E. Hill ◽  
Laura A. Lettice
Keyword(s):  
Long Range ◽  
Congenital Abnormalities ◽  
Limb Bud ◽  
Temporal Expression ◽  
Developmentally Regulated ◽  
Conserved Sequence ◽  
Regulatory Mutations ◽  
Spatio Temporal ◽  
Relationship Of ◽  
The Relationship

Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.

scholarly journals Experimentally Increased Codon Bias in the Drosophila Adh Gene Leads to an Increase in Larval, But Not Adult, Alcohol Dehydrogenase Activity

Genetics ◽  
2009 ◽  
Vol 184 (2) ◽  
pp. 547-555 ◽  
Author(s):  
Winfried Hense ◽  
Nathan Anderson ◽  
Stephan Hutter ◽  
Wolfgang Stephan ◽  
John Parsch ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Codon Bias ◽  
Alcohol Dehydrogenase Activity ◽  
Adh Gene ◽  
Drosophila Adh

Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning

2018 ◽  
Vol 97 (9) ◽  
pp. 1055-1063 ◽  
Author(s):  
H. Seo ◽  
T. Amano ◽  
R. Seki ◽  
T. Sagai ◽  
J. Kim ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Long Range ◽  
Sonic Hedgehog ◽  
Intergenic Region ◽  
Mouse Genome ◽  
The Novel ◽  
Targeted Deletion ◽  
Conserved Sequence

Sonic hedgehog ( Shh) is important in pattern formation during development. Shh transcription is modulated by a long-range regulatory mechanism containing a number of enhancers, which are spread over nearly 850 kb in the mouse genome. Shh enhancers in the nervous system have been found between intron and 430 kb upstream of Shh. Enhancers in the oral cavity, pharynx, lung, gut, and limbs have been discovered between 610 kb and 850 kb upstream of Shh. However, the intergenic region ranging from 430 to 610 kb upstream of Shh remains to be elucidated. In the present study, we found a novel long-range enhancer located 558 kb upstream of Shh. The enhancer showed in vivo activity in oral cavity and whiskers. A targeted deletion from the novel enhancer to mammal reptile conserved sequence 1 (MRCS1), which is a known enhancer of Shh in oral cavity, resulted in supernumerary molar formation, confirming the essential role of this intergenic region for Shh transcription in teeth. Furthermore, we clarified the binding of Lef1/Tcfs to the new enhancer and MRCS1, suggesting that Wnt/β-catenin signaling regulates Shh signaling in the oral cavity via these enhancers.

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