Reciprocal regulation of metabolic and signaling pathways

Andreas S. Barth, Ami Kumordzie, Carlo Colantuoni, Kenneth B. Margulies, Thomas P. Cappola, Gordon F. Tomaselli

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: By studying genome-wide expression patterns in healthy and diseased tissues across a wide range of pathophysiological conditions, DNA microarrays have revealed unique insights into complex diseases. However, the high-dimensionality of microarray data makes interpretation of heterogeneous gene expression studies inherently difficult.Results: Using a large-scale analysis of more than 40 microarray studies encompassing ~2400 mammalian tissue samples, we identified a common theme across heterogeneous microarray studies evident by a robust genome-wide inverse regulation of metabolic and cell signaling pathways: We found that upregulation of cell signaling pathways was invariably accompanied by downregulation of cell metabolic transcriptional activity (and vice versa). Several findings suggest that this characteristic gene expression pattern represents a new principle of mammalian transcriptional regulation. First, this coordinated transcriptional pattern occurred in a wide variety of physiological and pathophysiological conditions and was identified across all 20 human and animal tissue types examined. Second, the differences in metabolic gene expression predicted the magnitude of differences for signaling and all other pathways, i.e. tissue samples with similar expression levels of metabolic transcripts did not show any differences in gene expression for all other pathways. Third, this transcriptional pattern predicted a profound effect on the proteome, evident by differences in structure, stability and post-translational modifications of proteins belonging to signaling and metabolic pathways, respectively.Conclusions: Our data suggest that in a wide range of physiological and pathophysiological conditions, gene expression changes exhibit a recurring pattern along a transcriptional axis, characterized by an inverse regulation of major metabolic and cell signaling pathways. Given its widespread occurrence and its predicted effects on protein structure, protein stability and post-translational modifications, we propose a new principle for transcriptional regulation in mammalian biology.

Original languageEnglish (US)
Article number197
JournalBMC Genomics
Volume11
Issue number1
DOIs
StatePublished - Mar 24 2010
Externally publishedYes

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Metabolic Networks and Pathways
Gene Expression
Post Translational Protein Processing
Genome
Protein Stability
Proteome
Oligonucleotide Array Sequence Analysis
Up-Regulation
Down-Regulation
Proteins

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Barth, A. S., Kumordzie, A., Colantuoni, C., Margulies, K. B., Cappola, T. P., & Tomaselli, G. F. (2010). Reciprocal regulation of metabolic and signaling pathways. BMC Genomics, 11(1), [197]. https://doi.org/10.1186/1471-2164-11-197

Reciprocal regulation of metabolic and signaling pathways. / Barth, Andreas S.; Kumordzie, Ami; Colantuoni, Carlo; Margulies, Kenneth B.; Cappola, Thomas P.; Tomaselli, Gordon F.

In: BMC Genomics, Vol. 11, No. 1, 197, 24.03.2010.

Research output: Contribution to journalArticle

Barth, AS, Kumordzie, A, Colantuoni, C, Margulies, KB, Cappola, TP & Tomaselli, GF 2010, 'Reciprocal regulation of metabolic and signaling pathways', BMC Genomics, vol. 11, no. 1, 197. https://doi.org/10.1186/1471-2164-11-197
Barth AS, Kumordzie A, Colantuoni C, Margulies KB, Cappola TP, Tomaselli GF. Reciprocal regulation of metabolic and signaling pathways. BMC Genomics. 2010 Mar 24;11(1). 197. https://doi.org/10.1186/1471-2164-11-197
Barth, Andreas S. ; Kumordzie, Ami ; Colantuoni, Carlo ; Margulies, Kenneth B. ; Cappola, Thomas P. ; Tomaselli, Gordon F. / Reciprocal regulation of metabolic and signaling pathways. In: BMC Genomics. 2010 ; Vol. 11, No. 1.
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