TY - JOUR TI - Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii. AU - Lopez Garcia de Lomana, Adrian AU - Schauble, Sascha AU - Valenzuela, Jacob AU - Imam, Saheed AU - Carter, Warren AU - Bilgin, Damla D. AU - Yohn, Christopher B. AU - Turkarslan, Serdar AU - Reiss, David J. AU - Orellana, Monica V. AU - Price, Nathan D. AU - Baliga, Nitin S. T2 - Biotechnology for biofuels AB - 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. DA - 2015/// PY - 2015 DO - 10.1186/s13068-015-0391-z VL - 8 SP - 207 J2 - Biotechnol Biofuels LA - eng SN - 1754-6834 1754-6834 KW - Chlamydomonas reinhardtii KW - Metabolic network KW - Network modeling KW - Phenotypic transition KW - Transcriptional regulatory network KW - lipid accumulation ER -