Filling gaps in PPAR-alpha signaling through comparative nutrigenomics analysis

D. Cavalieri, E. Calura, C. Romualdi, E. Marchi, M. Radonjic, B. van Ommen, M.R. Müller

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

Background: The application of high-throughput genomic tools in nutrition research is a widespread practice. However, it is becoming increasingly clear that the outcome of individual expression studies is insufficient for the comprehensive understanding of such a complex field. Currently, the availability of the large amounts of expression data in public repositories has opened up new challenges on microarray data analyses. We have focused on PPAR alpha, a ligand-activated transcription factor functioning as fatty acid sensor controlling the gene expression regulation of a large set of genes in various metabolic organs such as liver, small intestine or heart. The function of PPAR alpha is strictly connected to the function of its target genes and, although many of these have already been identified, major elements of its physiological function remain to be uncovered. To further investigate the function of PPAR alpha, we have applied a cross-species meta-analysis approach to integrate sixteen microarray datasets studying high fat diet and PPAR alpha signal perturbations in different organisms. Results: We identified 164 genes (MDEGs) that were differentially expressed in a constant way in response to a high fat diet or to perturbations in PPARs signalling. In particular, we found five genes in yeast which were highly conserved and homologous of PPAR alpha targets in mammals, potential candidates to be used as models for the equivalent mammalian genes. Moreover, a screening of the MDEGs for all known transcription factor binding sites and the comparison with a human genome-wide screening of Peroxisome Proliferating Response Elements (PPRE), enabled us to identify, 20 new potential candidate genes that show, both binding site, both change in expression in the condition studied. Lastly, we found a non random localization of the differentially expressed genes in the genome. Conclusion: The results presented are potentially of great interest to resume the currently available expression data, exploiting the power of in silico analysis filtered by evolutionary conservation. The analysis enabled us to indicate potential gene candidates that could fill in the gaps with regards to the signalling of PPAR alpha and, moreover, the non-random localization of the differentially expressed genes in the genome, suggest that epigenetic mechanisms are of importance in the regulation of the transcription operated by PPAR alpha
Original languageEnglish
Article number596
Number of pages16
JournalBMC Genomics
Volume10
DOIs
Publication statusPublished - 2009

Keywords

  • proliferator-activated receptor
  • fatty-acid oxidation
  • 17-beta-hydroxysteroid-dehydrogenase type-iv
  • gene-expression data
  • coa synthase gene
  • nuclear receptors
  • null mice
  • saccharomyces-cerevisiae
  • interaction networks
  • binding protein

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