title: PipX, the coactivator of NtcA, is a global regulator in cyanobacteria.
abstract: To modulate the expression of genes involved in nitrogen assimilation, the cyanobacterial PII-interacting protein X (PipX) interacts with the global transcriptional regulator NtcA and the signal transduction protein PII, a protein found in all three domains of life as an integrator of signals of the nitrogen and carbon balance. PipX can form alternate complexes with NtcA and PII, and these interactions are stimulated and inhibited, respectively, by 2-oxoglutarate, providing a mechanistic link between PII signaling and NtcA-regulated gene expression. Here, we demonstrate that PipX is involved in a much wider interaction network. The effect of pipX alleles on transcript levels was studied by RNA sequencing of S. elongatus strains grown in the presence of either nitrate or ammonium, followed by multivariate analyses of relevant mutant/control comparisons. As a result of this process, 222 genes were classified into six coherent groups of differentially regulated genes, two of which, containing either NtcA-activated or NtcA-repressed genes, provided further insights into the function of NtcA-PipX complexes. The remaining four groups suggest the involvement of PipX in at least three NtcA-independent regulatory pathways. Our results pave the way to uncover new regulatory interactions and mechanisms in the control of gene expression in cyanobacteria.
authors.affiliation: División de Genética and.
authors.forename: Javier
authors.initials: J
authors.lastname: Espinosa
authors.affiliation: Departamento de Matemática Aplicada, Universidad de Alicante, 03080 Alicante, Spain;
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodríguez-Mateos
authors.affiliation: División de Genética and.
authors.forename: Paloma
authors.initials: P
authors.lastname: Salinas
authors.affiliation: Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria and Instituto de Biomedicina y Biotecnología de Cantabria, 39011 Santander, Spain; and.
authors.forename: Val F
authors.initials: VF
authors.lastname: Lanza
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
authors.forename: Ray
authors.initials: R
authors.lastname: Dixon
authors.affiliation: Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria and Instituto de Biomedicina y Biotecnología de Cantabria, 39011 Santander, Spain; and.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cruz
authors.affiliation: División de Genética and contrera@ua.es.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Contreras
mesh_terms: D064751:Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000145:classification; D015964:Gene Expression Regulation, Bacterial; D007656:Ketoglutaric Acids / Q000494:pharmacology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009154:Mutation; D009566:Nitrates / Q000378:metabolism / Q000494:pharmacology; D009584:Nitrogen / Q000378:metabolism / Q000494:pharmacology; D059372:Nucleotide Motifs / Q000235:genetics; D051922:PII Nitrogen Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012689:Sequence Homology, Nucleic Acid; D046940:Synechococcus / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D064751:Ammonium Compounds; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D007656:Ketoglutaric Acids; D009566:Nitrates; D051922:PII Nitrogen Regulatory Proteins; D014157:Transcription Factors; C075617:ntcA protein, Synechococcus; D009584:Nitrogen
keywords: nitrogen regulation; photosynthesis; transcription; translation