Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii.
Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii.
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DOI：
10.1186/s13068-015-0391-z
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发表时间：
2015
影响因子：
6.3
通讯作者：
Baliga NS
中科院分区：
文献类型：
--
作者：
López García de Lomana A;Schäuble S;Valenzuela J;Imam S;Carter W;Bilgin DD;Yohn CB;Turkarslan S;Reiss DJ;Orellana MV;Price ND;Baliga NS
藻类积累脂质以承受包括宏量营养素饥饿在内的各种环境胁迫。尽管这种反应已被广泛研究，但对控制转化为脂质积累的转录调控网络（TRN）的深入了解仍然难以捉摸。在这项研究中，我们使用了系统生物学的方法来阐明转录程序，该转录程序协调氮饥饿诱导的代谢调整，驱动莱茵衣藻的脂质积累。我们发现，氮饥饿触发了2147个转录本的差异调控，这些转录本在215个不同的模块中被共同调控，并被暂时排序为31个转录波。早期反应在12分钟内触发，通过激活关键信号通路启动生长停滞，同时通过调节运输过程和泛素介导的蛋白质降解为后期阶段准备细胞内环境。随后，中枢代谢和碳固定被重塑以触发三酰基甘油的积累。进一步的分析表明，这些全基因组转录事件的浪潮是由至少17个转录调控因子精心策划的调控程序协调的，其中许多转录调控因子以前并未涉及这一过程。我们证明TRN在近4小时的时间内协调57种代谢酶的转录下调，以驱动单位生物量脂质含量的增加。值得注意的是，这个TRN似乎也在硫饥饿期间驱动脂质积累，而磷饥饿诱导了不同的调节程序。这里描述的TRN模型可以在http://networks.systemsbiology.net/chlamy-portal上作为社区范围的网络资源获得。在这项工作中，我们发现了TRN控制从N饥饿到脂质积累转变的综合机制模型。该程序协调顺序有序的转录波，同时阻止生长并导致脂质积累。这项研究产生了预测工具，将有助于制定策略，合理操纵调节和代谢网络，以更好地生产生物燃料和生物质。本文的在线版本（doi:10.1186/s13068-015-0391-z）包含补充材料，仅供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/s13068-015-0391-z) contains supplementary material, which is available to authorized users.