title: Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii.
abstract: BACKGROUND
  Algae accumulate lipids to endure different kinds of environmental stresses including macronutrient starvation. Although this response has been extensively studied, an in depth understanding of the transcriptional regulatory network (TRN) that controls the transition into lipid accumulation remains elusive. In this study, we used a systems biology approach to elucidate the transcriptional program that coordinates the nitrogen starvation-induced metabolic readjustments that drive lipid accumulation in Chlamydomonas reinhardtii.
  
  
  RESULTS
  We demonstrate that nitrogen starvation triggered differential regulation of 2147 transcripts, which were co-regulated in 215 distinct modules and temporally ordered as 31 transcriptional waves. An early-stage response was triggered within 12 min that initiated growth arrest through activation of key signaling pathways, while simultaneously preparing the intracellular environment for later stages by modulating transport processes and ubiquitin-mediated protein degradation. Subsequently, central metabolism and carbon fixation were remodeled to trigger the accumulation of triacylglycerols. Further analysis revealed that these waves of genome-wide transcriptional events were coordinated by a regulatory program orchestrated by at least 17 transcriptional regulators, many of which had not been previously implicated in this process. We demonstrate that the TRN coordinates transcriptional downregulation of 57 metabolic enzymes across a period of nearly 4 h to drive an increase in lipid content per unit biomass. Notably, this TRN appears to also drive lipid accumulation during sulfur starvation, while phosphorus starvation induces a different regulatory program. The TRN model described here is available as a community-wide web-resource at http://networks.systemsbiology.net/chlamy-portal.
  
  
  CONCLUSIONS
  In this work, we have uncovered a comprehensive mechanistic model of the TRN controlling the transition from N starvation to lipid accumulation. The program coordinates sequentially ordered transcriptional waves that simultaneously arrest growth and lead to lipid accumulation. This study has generated predictive tools that will aid in devising strategies for the rational manipulation of regulatory and metabolic networks for better biofuel and biomass production.
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: Adrián
authors.initials: A
authors.lastname: López García de Lomana
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA ; Jena University Language and Information Engineering (JULIE) Lab, Friedrich-Schiller-University Jena, Jena, Germany ; Research Group Theoretical Systems Biology, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Schäuble
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Valenzuela
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: Saheed
authors.initials: S
authors.lastname: Imam
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Carter
authors.affiliation: Sapphire Energy Inc., San Diego, CA USA.
authors.forename: Damla D
authors.initials: DD
authors.lastname: Bilgin
authors.affiliation: Sapphire Energy Inc., San Diego, CA USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Yohn
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: Serdar
authors.initials: S
authors.lastname: Turkarslan
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiss
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA ; Polar Science Center, University of Washington, Seattle, WA USA.
authors.forename: Mónica V
authors.initials: MV
authors.lastname: Orellana
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA ; Departments of Bioengineering and Computer Science and Engineering, University of Washington, Seattle, WA USA ; Molecular and Cellular Biology Program, University of Washington, Seattle, WA USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Price
authors.affiliation: Institute for Systems Biology, 401 Terry Ave N, Seattle, 98109 WA USA ; Departments of Biology and Microbiology, University of Washington, Seattle, WA USA ; Molecular and Cellular Biology Program, University of Washington, Seattle, WA USA ; Lawrence Berkeley National Lab, Berkeley, CA USA.
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
keywords: Chlamydomonas reinhardtii; Lipid accumulation; Metabolic network; Network modeling; Phenotypic transition; Transcriptional regulatory network