Deciphering the transcriptional regulatory logic of amino acid metabolism.

TitleDeciphering the transcriptional regulatory logic of amino acid metabolism.
Publication TypeJournal Article
Year of Publication2011
AuthorsCho B-K, Federowicz S, Park Y-S, Zengler K, Palsson BØ
JournalNat Chem Biol
Volume8
Issue1
Pagination65-71
PubMed Date11/2011
ISSN1552-4469
KeywordsAmino Acids, Escherichia coli, Gene Expression Regulation, Genome-Wide Association Study, Transcription Factors, Transcription, Genetic
Abstract

Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and gene expression data for the transcription factors ArgR, Lrp and TrpR showed that 19 out of 20 amino acid biosynthetic pathways are either directly or indirectly controlled by these regulators. Classifying the regulated genes into three functional categories of transport, biosynthesis and metabolism leads to the elucidation of regulatory motifs that constitute the integrated network's basic building blocks. The regulatory logic of these motifs was determined on the basis of relationships between transcription factor binding and changes in the amount of transcript in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules, revealing the overarching regulatory principles of the amino acid stimulon.

Alternate JournalNat. Chem. Biol.
PubMed ID22082910
PubMed Central IDPMC3777760
Grant ListGM062791 / GM / NIGMS NIH HHS / United States
R01 GM062791 / GM / NIGMS NIH HHS / United States

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