Computational Prediction and Validation of BAHD1 as a Novel Molecule for Ulcerative Colitis

Sci Rep. 2015 Jul 17:5:12227. doi: 10.1038/srep12227.

Abstract

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / metabolism
  • Computer Simulation
  • Disease Models, Animal
  • Gene Expression
  • Gene Knockout Techniques
  • Genetic Predisposition to Disease*
  • Humans
  • I-kappa B Proteins / antagonists & inhibitors
  • I-kappa B Proteins / metabolism
  • Inflammation Mediators / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Models, Biological*
  • NF-kappa B / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Reproducibility of Results
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • BAHD1 protein, human
  • BAHD1 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • I-kappa B Proteins
  • Inflammation Mediators
  • NF-kappa B
  • RNA, Small Interfering
  • Receptors, Tumor Necrosis Factor, Type I
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases