title: In silico analysis of T-bet activity in peripheral blood mononuclear cells in patients with inflammatory bowel disease (IBD).
abstract: T-bet (TBX21) is a transcription factor that regulates T-cell differentiation, and has recently been implicated in the pathogenesis of Crohn's disease (CD). The regulatory networks through which T-bet affects immune function are unknown. An NCBI gene expression profile from patients with CD and controls was analyzed. T-bet transcription factor binding sites and promoter modules were identified using promoter analysis software. Functional correlations between T-bet-containing promoters were determined using data mining and ontological analysis. T-bet expression in CD peripheral blood mononuclear cells (PBMCs) (n=59) was significantly reduced compared to control (n=42) (p<0.0001) and ulcerative colitis PBMCs (n=26), (p=0.005). The promoter regions of all genes differentially-expressed in CD were probed for T-bet Transcription Factor Binding Sites (TFBSs). Twenty-three genes contained transcription-factor binding sites for T-bet; 8 were down-regulated, and 15 were up-regulated in CD-PBMCs. Three genes (S100A16, ABHD3 and EZH1) that were down-regulated in CD-PBMCs contained a complex promoter module consisting of T-bet and EGRF transcription-factor binding sites. Ontological analysis revealed that a significant number of differentially-expressed genes that contain T-bet binding sites are involved in innate immunity (8 genes, Z-score 4.11) and signal transduction (5 genes, Z-score 2.65). This combination of gene expression datasets and promoter analysis has identified a network of genes that contain simple T-bet binding sites, and complex T-bet promoter modules, in their promoter regions. These results implicate a mechanism through which T-bet may influence innate immunity in CD.
authors.affiliation: School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Nielsen Q
authors.initials: NQ
authors.lastname: Fernandez-Becker
authors.forename: Alan C
authors.initials: AC
authors.lastname: Moss
mesh_terms: D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics; D003198:Computer Simulation; D003424:Crohn Disease / Q000097:blood / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor