title: Ni induces the CRR1-dependent regulon revealing overlap and distinction between hypoxia and Cu deficiency responses in Chlamydomonas reinhardtii.
abstract: The selectivity of metal sensors for a single metal ion is critical for cellular metal homeostasis. A suite of metal-responsive regulators is required to maintain a prescribed balance of metal ions ensuring that each apo-protein binds the correct metal. However, there are cases when non-essential metals ions disrupt proper metal sensing. An analysis of the Ni-responsive transcriptome of the green alga Chlamydomonas reinhardtii reveals that Ni artificially turns on the CRR1-dependent Cu-response regulon. Since this regulon also responds to hypoxia, a combinatorial transcriptome analysis was leveraged to gain insight into the mechanisms by which Ni interferes with the homeostatic regulation of Cu and oxygen status. Based on parallels with the effect of Ni on the hypoxic response in animals, we propose that a possible link between Cu, oxygen and Ni sensing is an as yet uncharacterized prolyl hydroxylase that regulates a co-activator of CRR1. This analysis also identified transcriptional responses to the pharmacological activation of the Cu-deficiency regulon. Although the Ni-responsive CRR1 regulon is composed of 56 genes (defined as the primary response), 259 transcripts responded to Ni treatment only when a copy of the wild-type CRR1 gene was present. The genome-wide impact of CRR1 target genes on the transcriptome was also evident from the 210 transcripts that were at least 2-fold higher in the crr1 strain, where the abundance of many CRR1 targets was suppressed. Additionally, we identified 120 transcripts that responded to Ni independent of CRR1 function. The putative functions of the proteins encoded by these transcripts suggest that high Ni results in protein damage.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. merchant@chem.ucla.edu.
authors.forename: Crysten E
authors.initials: CE
authors.lastname: Blaby-Haas
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. merchant@chem.ucla.edu.
authors.forename: Madeli
authors.initials: M
authors.lastname: Castruita
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. merchant@chem.ucla.edu and Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Sorel T
authors.initials: ST
authors.lastname: Fitz-Gibbon
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. merchant@chem.ucla.edu.
authors.forename: Janette
authors.initials: J
authors.lastname: Kropat
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. merchant@chem.ucla.edu and Institute for Genomics and Proteomics, University of California, Los Angeles, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: Sabeeha S
authors.initials: SS
authors.lastname: Merchant
mesh_terms: D016825:Chlamydomonas reinhardtii / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000172:deficiency*; D018506:Gene Expression Regulation, Plant / Q000187:drug effects*; D006706:Homeostasis; D000860:Hypoxia; D009532:Nickel / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010940:Plant Proteins / Q000378:metabolism*; D018085:Regulon / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
chemical_list: D010940:Plant Proteins; D014157:Transcription Factors; D003300:Copper; D009532:Nickel; D010100:Oxygen