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  Transcriptional effects of a positive feedback circuit in Drosophila melanogaster

Bryk, J., Reeves, R. G., Reed, F. A., & Denton, J. A. (2017). Transcriptional effects of a positive feedback circuit in Drosophila melanogaster. BMC Genomics, 18: 990. doi:10.1186/s12864-017-4385-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-3E7B-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-1F5E-1
Genre: Journal Article

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Bryk, Jarosław, Author
Reeves, R. Guy1, Author              
Reed, Floyd A., Author
Denton, Jai A., Author
Affiliations:
1Research Group Population Genetics, Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445646              

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Free keywords: chlortetracycline; doxycycline; oxytetracycline; tetracycline; transactivator protein, adult; Article; controlled study; crop pest; disease carrier; DNA integration; Drosophila melanogaster; feedback system; female; gene; gene expression; gene locus; genome; larval stage; lethality; male; microarray analysis; nonhuman; transcriptomics; transgenic animal; transgenics; tTAV gene
 Abstract: Background: Synthetic systems that use positive feedback have been developed to control human disease vectors and crop pests. The tTAV system, which has been deployed in several insect species, relies on a positive feedback circuit that can be inhibited via dietary tetracycline. Although insects carrying tTAV fail to survive until adulthood in the absence of tetracycline, the exact reason for its lethality, as well as the transcriptomic effects of an active positive feedback circuit, remain unknown. Results: We engineered the tTAV system in Drosophila melanogaster and investigated the effects of tTAV genome integration locus on the whole fly transcriptome during larval and adult life stages in four transgenic fly strains using gene expression microarrays. We found that while there were widespread effects on the transcriptome, the gene expression differences after removal of tetracycline were not consistent between integration sites. No specific region of the genome was affected, no common set of genes or pathways, nor did the integration site affect the transcripts in cis. Conclusion: Although the positive feedback tTAV system is effective at killing insect larvae regardless of where it is inserted in the genome, it does not exhibit a specific, consistent transcriptional signature. Instead, each insertion site is associated with broad, but different, transcriptional effects. Our results suggest that lethality may not be caused by a direct effect on transcription of a set of key genes or pathways. Instead, we propose that rather than a specific action of a tTAV protein, it is the stochastic transcriptional effects specific to each insertion site that contribute to the tTAV-induced mortality. © 2017 The Author(s).

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Language(s): eng - English
 Dates: 2017-07-262017-12-152017-12-282017
 Publication Status: Published in print
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 Identifiers: DOI: 10.1186/s12864-017-4385-z
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Title: BMC Genomics
Source Genre: Journal
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Publ. Info: BioMed Central
Pages: - Volume / Issue: 18 Sequence Number: 990 Start / End Page: - Identifier: ISSN: 1471-2164
CoNE: https://pure.mpg.de/cone/journals/resource/111000136905010