Induction of a detoxification gene in Drosophila melanogaster requires an interaction between tissue specific enhancers and a novel cis-regulatory element.

Chung, Henry; Boey, Adrian; Lumb, Chris; Willoughby, Lee; Batterham, Philip; Daborn, Phillip J

Chung, Henry; Boey, Adrian; Lumb, Chris; Willoughby, Lee; Batterham, Philip; Daborn, Phillip J.

Afiliación

Chung H; Department of Genetics, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.

Insect Biochem Mol Biol ; 41(11): 863-71, 2011 Nov.

Article en En | MEDLINE | ID: mdl-21807095

RESUMEN

Organisms induce the expression of detoxification enzymes such as cytochrome P450s to deal with xenobiotics encountered in the environment. Research using cell culture systems has identified some of the cis-regulatory elements (CREs) and transcription factors involved in the induction of P450 genes in response to xenobiotic challenges. It was recently found that the CREs required for the basal expression of some P450s are distinct from the CREs involved in their induction. How these CREs mediate induction to xenobiotics in a tissue specific manner is not known. In this paper we show that, in Drosophila melanogaster, the induction response of the P450 gene Cyp6g1 to the xenobiotic Phenobarbital (PB) requires the presence of both tissue specific enhancers and a distinct CRE. The CRE does not drive gene expression but is required for the induction response. Site-directed mutagenesis of sequences within the CRE, sequences similar to mouse PB induction sequences, reduces the level of induction by PB, suggesting some degree of mechanistic conservation between flies and mice. This CRE may represent a unique class of CREs that has no inherent role in the basal transcriptional activity of genes, but is required for induction responses. Variations within this class of CREs may explain the variability of gene induction responses.

Asunto(s)

Sistema Enzimático del Citocromo P-450/metabolismo; Proteínas de Drosophila/metabolismo; Drosophila melanogaster/metabolismo; Regulación de la Expresión Génica; Animales; Sistema Enzimático del Citocromo P-450/genética; Proteínas de Drosophila/genética; Drosophila melanogaster/genética; Factores de Transcripción GATA/metabolismo; Tracto Gastrointestinal/metabolismo; Larva/metabolismo; Túbulos de Malpighi/metabolismo; Ratones; Fenobarbital; Elementos Reguladores de la Transcripción; Xenobióticos

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Sistema Enzimático del Citocromo P-450 / Proteínas de Drosophila / Drosophila melanogaster Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Insect Biochem Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2011 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido

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