TY - JOUR
T1 - Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii
AU - López García De Lomana, Adrián
AU - Schäuble, 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, Mónica V.
AU - Price, Nathan D.
AU - Baliga, Nitin S.
N1 - Funding Information:
Robinson and Chris Lausted for useful comments. This work was partially funded by DOE-ABY (DEEE0006315) (SI, JV, ALGL, WC, NSB, NDP), NIH Center for Systems Biology (grant P50 GM076547) (ALGL, NSB, NDP) and the Camille Dreyfus Teacher-Scholar program (NDP). We also acknowledge financial support from the German Ministry for Research and Education within the framework of the GerontoSys (grant FKZ 0315581D) and e:Med (grant FKZ 01ZX1402C) initiative (SS).
Publisher Copyright:
© 2015 López García de Lomana et al.
PY - 2015/12/2
Y1 - 2015/12/2
N2 - 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.
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.
KW - Chlamydomonas reinhardtii
KW - Lipid accumulation
KW - Metabolic network
KW - Network modeling
KW - Phenotypic transition
KW - Transcriptional regulatory network
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U2 - 10.1186/s13068-015-0391-z
DO - 10.1186/s13068-015-0391-z
M3 - Article
AN - SCOPUS:84949437000
VL - 8
JO - Biotechnology for Biofuels
JF - Biotechnology for Biofuels
SN - 1754-6834
IS - 1
M1 - 207
ER -