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Identification of key mechanisms controlling gene expression inLeishmaniainfected macrophages using genome-wide promoter analysis

Authors
Journal
Infection Genetics and Evolution
1567-1348
Publisher
Elsevier
Publication Date
Volume
11
Issue
4
Identifiers
DOI: 10.1016/j.meegid.2010.10.015
Keywords
  • Tfs
  • Tfbss
  • Promoters
  • Phylogenetic Foot Printing
  • Orthology
  • Tsss
  • Gene Regulation
  • Chip-Seq
  • Microarray Analysis
Disciplines
  • Computer Science

Abstract

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.

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