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Identification of key mechanisms controlling gene expression in Leishmania infected macrophages using genome-wide promoter analysis.

Identifieur interne : 000115 ( Main/Exploration ); précédent : 000114; suivant : 000116

Identification of key mechanisms controlling gene expression in Leishmania infected macrophages using genome-wide promoter analysis.

Auteurs : Kais Ghedira [Tunisie] ; Klaus Hornischer ; Tatiana Konovalova ; Ahmed-Zaki Jenhani ; Alia Benkahla ; Alexander Kel

Source :

RBID : pubmed:21093613

Descripteurs français

English descriptors

Abstract

The present study describes the in silico prediction of the regulatory network of Leishmania infected human macrophages. The construction of the gene regulatory network requires the identification of Transcription Factor Binding Sites (TFBSs) in the regulatory regions (promoters, enhancers) of genes that are regulated upon Leishmania infection. The promoters of human, mouse, rat, dog and chimpanzee genes were first identified in the whole genomes using available experimental data on full length cDNA sequences or deep CAGE tag data (DBTSS, FANTOM3, FANTOM4), mRNA models (ENSEMBL), or using hand annotated data (EPD, TRANSFAC). A phylogenetic footprinting analysis and a MATCH analysis of the promoter sequences were then performed to predict TFBS. Then, an SQL database that integrates all results of promoter analysis as well as other genome annotation information obtained from ENSEMBL, TRANSFAC, TRED (Transcription Regulatory Element Database), ORegAnno and the ENCODE project, was established. Finally publicly available expression data from human Leishmania infected macrophages were analyzed using the genome-wide information on predicted TFBS with the computer system ExPlain™. The gene regulatory network was constructed and activated signal transduction pathways were revealed. The Irak1 pathway was identified as a key pathway regulating gene expression changes in Leishmania infected macrophages.

DOI: 10.1016/j.meegid.2010.10.015
PubMed: 21093613


Affiliations:


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Le document en format XML

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<term>Binding Sites (genetics)</term>
<term>Computational Biology (MeSH)</term>
<term>Databases, Genetic (MeSH)</term>
<term>Dogs (MeSH)</term>
<term>Gene Expression Profiling (MeSH)</term>
<term>Gene Expression Regulation (MeSH)</term>
<term>Gene Regulatory Networks (genetics)</term>
<term>Genome-Wide Association Study (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Leishmania (physiology)</term>
<term>Leishmaniasis (physiopathology)</term>
<term>Macrophages (metabolism)</term>
<term>Macrophages (parasitology)</term>
<term>Metabolic Networks and Pathways (genetics)</term>
<term>Mice (MeSH)</term>
<term>Pan troglodytes (MeSH)</term>
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<term>Rats (MeSH)</term>
<term>Transcription Factors (metabolism)</term>
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<term>Analyse de profil d'expression de gènes (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Bases de données génétiques (MeSH)</term>
<term>Biologie informatique (MeSH)</term>
<term>Chiens (MeSH)</term>
<term>Facteurs de transcription (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Leishmania (physiologie)</term>
<term>Leishmaniose (physiopathologie)</term>
<term>Macrophages (métabolisme)</term>
<term>Macrophages (parasitologie)</term>
<term>Pan troglodytes (MeSH)</term>
<term>Rats (MeSH)</term>
<term>Régions promotrices (génétique) (génétique)</term>
<term>Régulation de l'expression des gènes (MeSH)</term>
<term>Réseaux de régulation génique (génétique)</term>
<term>Sites de fixation (génétique)</term>
<term>Souris (MeSH)</term>
<term>Voies et réseaux métaboliques (génétique)</term>
<term>Étude d'association pangénomique (MeSH)</term>
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<term>Gene Regulatory Networks</term>
<term>Metabolic Networks and Pathways</term>
<term>Promoter Regions, Genetic</term>
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<term>Sites de fixation</term>
<term>Voies et réseaux métaboliques</term>
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<term>Macrophages</term>
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<term>Leishmania</term>
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<term>Chiens</term>
<term>Humains</term>
<term>Pan troglodytes</term>
<term>Rats</term>
<term>Régulation de l'expression des gènes</term>
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<front>
<div type="abstract" xml:lang="en">The present study describes the in silico prediction of the regulatory network of Leishmania infected human macrophages. The construction of the gene regulatory network requires the identification of Transcription Factor Binding Sites (TFBSs) in the regulatory regions (promoters, enhancers) of genes that are regulated upon Leishmania infection. The promoters of human, mouse, rat, dog and chimpanzee genes were first identified in the whole genomes using available experimental data on full length cDNA sequences or deep CAGE tag data (DBTSS, FANTOM3, FANTOM4), mRNA models (ENSEMBL), or using hand annotated data (EPD, TRANSFAC). A phylogenetic footprinting analysis and a MATCH analysis of the promoter sequences were then performed to predict TFBS. Then, an SQL database that integrates all results of promoter analysis as well as other genome annotation information obtained from ENSEMBL, TRANSFAC, TRED (Transcription Regulatory Element Database), ORegAnno and the ENCODE project, was established. Finally publicly available expression data from human Leishmania infected macrophages were analyzed using the genome-wide information on predicted TFBS with the computer system ExPlain™. The gene regulatory network was constructed and activated signal transduction pathways were revealed. The Irak1 pathway was identified as a key pathway regulating gene expression changes in Leishmania infected macrophages.</div>
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