Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1

Rodrigo A. Gutiérrez, Trevor L. Stokes, Karen Thum, Xiaodong Xu, Mariana Obertello, Manpreet S. Katari, Milos Tanurdzic, Alexis Dean, Damion C. Nero, C. Robertson McClung, Gloria M. Coruzzi

Research output: Contribution to journalArticlepeer-review


Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of MSX, an inhibitor of glutamine synthetase, resulting in a block of Glu/Gln synthesis. Genes that responded to organic N were identified as those whose response to ammonium nitrate treatment was blocked in the presence of MSX. We showed that some genes previously identified to be regulated by nitrate are under the control of an organic N-metabolite. Using an integrated network model of molecular interactions, we uncovered a subnetwork regulated by organic N that included CCA1 and target genes involved in N-assimilation. We validated some of the predicted interactions and showed that regulation of the master clock control gene CCA1 by Glu or a Glu-derived metabolite in turn regulates the expression of key N-assimilatory genes. Phase response curve analysis shows that distinct N-metabolites can advance or delay the CCA1 phase. Regulation of CCA1 by organic N signals may represent a novel input mechanism for N-nutrients to affect plant circadian clock function.

Original languageEnglish (US)
Pages (from-to)4939-4944
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 25 2008


  • Circadian
  • Gene networks
  • Glutamate
  • Metabolism

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1'. Together they form a unique fingerprint.

Cite this