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Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

Publication ,  Journal Article
Todor, H; Sharma, K; Pittman, AMC; Schmid, AK
Published in: Nucleic acids research
October 2013

Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

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Published In

Nucleic acids research

DOI

EISSN

1362-4962

ISSN

0305-1048

Publication Date

October 2013

Volume

41

Issue

18

Start / End Page

8546 / 8558

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Promoter Regions, Genetic
  • Phosphotransferases (Paired Acceptors)
  • Halobacterium salinarum
  • Glucose
  • Gene Regulatory Networks
  • Gene Expression Regulation, Archaeal
  • Developmental Biology
  • Archaeal Proteins
 

Citation

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Todor, H., Sharma, K., Pittman, A. M. C., & Schmid, A. K. (2013). Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea. Nucleic Acids Research, 41(18), 8546–8558. https://doi.org/10.1093/nar/gkt659
Todor, Horia, Kriti Sharma, Adrianne M. C. Pittman, and Amy K. Schmid. “Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.Nucleic Acids Research 41, no. 18 (October 2013): 8546–58. https://doi.org/10.1093/nar/gkt659.
Todor H, Sharma K, Pittman AMC, Schmid AK. Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea. Nucleic acids research. 2013 Oct;41(18):8546–58.
Todor, Horia, et al. “Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.Nucleic Acids Research, vol. 41, no. 18, Oct. 2013, pp. 8546–58. Epmc, doi:10.1093/nar/gkt659.
Todor H, Sharma K, Pittman AMC, Schmid AK. Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea. Nucleic acids research. 2013 Oct;41(18):8546–8558.
Journal cover image

Published In

Nucleic acids research

DOI

EISSN

1362-4962

ISSN

0305-1048

Publication Date

October 2013

Volume

41

Issue

18

Start / End Page

8546 / 8558

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Promoter Regions, Genetic
  • Phosphotransferases (Paired Acceptors)
  • Halobacterium salinarum
  • Glucose
  • Gene Regulatory Networks
  • Gene Expression Regulation, Archaeal
  • Developmental Biology
  • Archaeal Proteins