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 that were differentially expressed in a constant way in response to a high fat diet or to perturbations in PPARs signalling. The analysis enabled us to suggest potential gene candidates that could fill in the gaps with regards to the signalling of PPAR-alpha. In particular, we found five differentially expressed 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 comparison of the differentially expressed genes with a genome-wide screening of Peroxisome Proliferating Response Elements (PPRE), enabled us to identify, 3 new potential candidate mouse genes (Slc25a42, Acsl3, Creb3l3) 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, suggesting that epigenetic mechanisms are of importance in the regulation of the transcription operated by PPAR-alpha. 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.

Filling gaps in PPAR-alpha signaling through comparative nutrigenomics analysis / Cavalieri D.; Calura E.; Romualdi C.; Marchi E.; Radonjic M.; van Ommen B.; Muller M.. - In: BMC GENOMICS. - ISSN 1471-2164. - STAMPA. - 10:(2009), pp. 596-....

Filling gaps in PPAR-alpha signaling through comparative nutrigenomics analysis

CAVALIERI, DUCCIO;MARCHI, EMMANUELA;
2009

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 that were differentially expressed in a constant way in response to a high fat diet or to perturbations in PPARs signalling. The analysis enabled us to suggest potential gene candidates that could fill in the gaps with regards to the signalling of PPAR-alpha. In particular, we found five differentially expressed 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 comparison of the differentially expressed genes with a genome-wide screening of Peroxisome Proliferating Response Elements (PPRE), enabled us to identify, 3 new potential candidate mouse genes (Slc25a42, Acsl3, Creb3l3) 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, suggesting that epigenetic mechanisms are of importance in the regulation of the transcription operated by PPAR-alpha. 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.
2009
10
596
...
Cavalieri D.; Calura E.; Romualdi C.; Marchi E.; Radonjic M.; van Ommen B.; Muller M.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/368326
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