title: Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1.
abstract: 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.
authors.affiliation: Department of Biology, New York University, 100 Washington Square East, 1009 Main Building, New York, NY 10003, USA.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Gutiérrez
authors.forename: Trevor L
authors.initials: TL
authors.lastname: Stokes
authors.forename: Karen
authors.initials: K
authors.lastname: Thum
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
authors.forename: Mariana
authors.initials: M
authors.lastname: Obertello
authors.forename: Manpreet S
authors.initials: MS
authors.lastname: Katari
authors.forename: Milos
authors.initials: M
authors.lastname: Tanurdzic
authors.forename: Alexis
authors.initials: A
authors.lastname: Dean
authors.forename: Damion C
authors.initials: DC
authors.lastname: Nero
authors.forename: C Robertson
authors.initials: CR
authors.lastname: McClung
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Coruzzi
mesh_terms: D017360:Arabidopsis / Q000187:drug effects* / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000187:drug effects; D018506:Gene Expression Regulation, Plant / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D018745:Genome, Plant; D018698:Glutamic Acid / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D008957:Models, Genetic; D009566:Nitrates / Q000494:pharmacology; D009584:Nitrogen / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D036226:Seedlings / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; C114425:CCA1 protein, Arabidopsis; D009566:Nitrates; D012333:RNA, Messenger; D014157:Transcription Factors; D005973:Glutamine; D018698:Glutamic Acid; D009584:Nitrogen; C006568:ammonium nitrate