Transcription Factor Binding Site Enrichment Analysis in Co-Expression Modules in Celiac Disease

Genes
Irati Romero-GarmendiaJose Ramon Bilbao

Abstract

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gli...Continue Reading

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Datasets Mentioned

BETA
E-MEXP-1823

Methods Mentioned

BETA
biopsies
nuclear
biopsy
Protein Assay
electrophoresis
nuclear translocation

Software Mentioned

R package WGCNA
UCSC genome browser
DCGL R package
GraphPad Prism
Babelomics
FatiGO
BLAST

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