Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network

Nat Biotechnol. 2008 Nov;26(11):1251-9. doi: 10.1038/nbt.1499.

Abstract

Significant insight about biological networks arises from the study of network motifs--overly abundant network subgraphs--but such wiring patterns do not specify when and how potential routes within a cellular network are used. To address this limitation, we introduce activity motifs, which capture patterns in the dynamic use of a network. Using this framework to analyze transcription in Saccharomyces cerevisiae metabolism, we find that cells use different timing activity motifs to optimize transcription timing in response to changing conditions: forward activation to produce metabolic compounds efficiently, backward shutoff to rapidly stop production of a detrimental product and synchronized activation for co-production of metabolites required for the same reaction. Measuring protein abundance over a time course reveals that mRNA timing motifs also occur at the protein level. Timing motifs significantly overlap with binding activity motifs, where genes in a linear chain have ordered binding affinity to a transcription factor, suggesting a mechanism for ordered transcription. Finely timed transcriptional regulation is therefore abundant in yeast metabolism, optimizing the organism's adaptation to new environmental conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Glycerol* / metabolism
  • Metabolic Networks and Pathways
  • Pentose Phosphate Pathway*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Time Factors
  • Transcription, Genetic*

Substances

  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Glycerol

Associated data

  • GEO/GSE13219