title: Identification of key mechanisms controlling gene expression in Leishmania infected macrophages using genome-wide promoter analysis.
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.
authors.affiliation: Laboratory of Immunology, Vaccinology, and Molecular Genetics, Institut Pasteur de Tunis, 13 place Pasteur BP 74, Tunis, Tunisia.
authors.forename: Kais
authors.initials: K
authors.lastname: Ghedira
authors.forename: Klaus
authors.initials: K
authors.lastname: Hornischer
authors.forename: Tatiana
authors.initials: T
authors.lastname: Konovalova
authors.forename: Ahmed-Zaki
authors.initials: AZ
authors.lastname: Jenhani
authors.forename: Alia
authors.initials: A
authors.lastname: Benkahla
authors.forename: Alexander
authors.initials: A
authors.lastname: Kel
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D030541:Databases, Genetic; D004285:Dogs; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007891:Leishmania / Q000502:physiology; D007896:Leishmaniasis / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D002679:Pan troglodytes; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors