title: Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii.
abstract: Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combined omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. Evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism.
authors.affiliation: Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Gargouri
authors.affiliation: Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Jeong-Jin
authors.initials: JJ
authors.lastname: Park
authors.affiliation: College of Agricultural, Consumer and Environmental Sciences, New Mexico State University, 1780 E. University Ave, Las Cruces, NM 88003, USA.
authors.forename: F Omar
authors.initials: FO
authors.lastname: Holguin
authors.affiliation: Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Donald Danforth Plant Science Center, 975 North Warson Road, St Louis, MO 63132, USA Current address: National Center of Biomedical Analysis, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Plant Biology, Michigan State University, 612 Wilson Road, East Lansing, MI 48864, USA.
authors.forename: Rahul R
authors.initials: RR
authors.lastname: Deshpande
authors.affiliation: Department of Plant Biology, Michigan State University, 612 Wilson Road, East Lansing, MI 48864, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Shachar-Hill
authors.affiliation: Donald Danforth Plant Science Center, 975 North Warson Road, St Louis, MO 63132, USA Department of Chemistry, University of North Carolina at Chapel Hill, 125 South Road, Chapel Hill, NC 27516, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Hicks
authors.affiliation: Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA gangd@wsu.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Gang
mesh_terms: D020418:Algal Proteins / Q000235:genetics / Q000378:metabolism; D016825:Chlamydomonas reinhardtii / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016678:Genome; D050356:Lipid Metabolism; D055442:Metabolome; D009584:Nitrogen / Q000172:deficiency*; D020543:Proteome; D059467:Transcriptome
chemical_list: D020418:Algal Proteins; D020543:Proteome; D009584:Nitrogen
keywords: Biofuel; Chlamydomonas reinhardtii; RNA-seq; metabolomics; network analysis; proteomics; regulatory hubs; transcription factors; transcriptional regulators.