1887

Abstract

N-Lysine acetylation is a dynamic, reversible and regulatory post-translational modification (PTM) in prokaryotes, which integrates and coordinates metabolisms responding to environmental clues. However, the molecular mechanism underlying the signalling pathway from nutrient sensing to protein acetylation remains incompletely understood in micro-organisms. Here we found that global nitrogen regulator GlnR directly controls transcription of genes encoding lysine deacetylases in Actinobacteria. Electrophoretic mobility shift assays and real-time PCR (RT-PCR) in three Actinobacteria species (, and ) revealed that GlnR regulator protein is able to interact with the promoter regions of these genes and activate their transcription. Furthermore, it was demonstrated that cellular acetylation status (acetylome) is modulated by extracellular nitrogen availability. Our results present an example of the novel complete signal transduction mechanism of regulating protein deacetylation through a nutrient-sensing pleiotropic regulator in response to nutrient availability.

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2017-11-01
2024-12-08
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References

  1. Grundy FJ, Turinsky AJ, Henkin TM. Catabolite regulation of Bacillus subtilis acetate and acetoin utilization genes by CcpA. J Bacteriol 1994; 176:4527–4533 [View Article][PubMed]
    [Google Scholar]
  2. Castaño-Cerezo S, Bernal V, Blanco-Catalá J, Iborra JL, Cánovas M. cAMP-CRP co-ordinates the expression of the protein acetylation pathway with central metabolism in Escherichia coli. Mol Microbiol 2011; 82:1110–1128 [View Article][PubMed]
    [Google Scholar]
  3. Hentchel KL, Thao S, Intile PJ, Escalante-Semerena JC. Deciphering the regulatory circuitry that controls reversible lysine acetylation in Salmonella enterica. MBio 2015; 6:e00891-15 [View Article][PubMed]
    [Google Scholar]
  4. Hodawadekar SC, Marmorstein R. Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene 2007; 26:5528–5540 [View Article][PubMed]
    [Google Scholar]
  5. Noriega LG, Feige JN, Canto C, Yamamoto H, Yu J et al. CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability. EMBO Rep 2011; 12:1069–1076 [View Article][PubMed]
    [Google Scholar]
  6. Xiong S, Salazar G, Patrushev N, Alexander RW. FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 2011; 286:5289–5299 [View Article][PubMed]
    [Google Scholar]
  7. Jenkins VA, Barton GR, Robertson BD, Williams KJ. Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis. BMC Genomics 2013; 14:301 [View Article][PubMed]
    [Google Scholar]
  8. You D, Wang MM, Ye BC. Acetyl-CoA synthetases of Saccharopolyspora erythraea are regulated by the nitrogen response regulator GlnR at both transcriptional and post-translational levels. Mol Microbiol 2017; 103:845–859 [View Article][PubMed]
    [Google Scholar]
  9. You D, Yin BC, Li ZH, Zhou Y, Yu WB et al. Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism. Proc Natl Acad Sci USA 2016; 113:6653–6658 [View Article][PubMed]
    [Google Scholar]
  10. Neilson KA, Ali NA, Muralidharan S, Mirzaei M, Mariani M et al. Less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics 2011; 11:535–553 [View Article][PubMed]
    [Google Scholar]
  11. Yao LL, Liao CH, Huang G, Zhou Y, Rigali S et al. GlnR-mediated regulation of nitrogen metabolism in the actinomycete Saccharopolyspora erythraea. Appl Microbiol Biotechnol 2014; 98:7935–7948 [View Article][PubMed]
    [Google Scholar]
  12. Liao CH, Yao LL, Ye BC. Three genes encoding citrate synthases in Saccharopolyspora erythraea are regulated by the global nutrient-sensing regulators GlnR, DasR, and CRP. Mol Microbiol 2014; 94:1065–1084 [View Article][PubMed]
    [Google Scholar]
  13. Hentchel KL, Escalante-Semerena JC. Acylation of biomolecules in prokaryotes: a widespread strategy for the control of biological function and metabolic stress. Microbiol Mol Biol Rev 2015; 79:321–346 [View Article][PubMed]
    [Google Scholar]
  14. Starai VJ, Celic I, Cole RN, Boeke JD, Escalante-Semerena JC. Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science 2002; 298:2390–2392 [View Article][PubMed]
    [Google Scholar]
  15. Gardner JG, Escalante-Semerena JC. In Bacillus subtilis, the sirtuin protein deacetylase, encoded by the srtN gene (formerly yhdZ), and functions encoded by the acuABC genes control the activity of acetyl coenzyme A synthetase. J Bacteriol 2009; 191:1749–1755 [View Article][PubMed]
    [Google Scholar]
  16. Rigali S, Nothaft H, Noens EE, Schlicht M, Colson S et al. The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development. Mol Microbiol 2006; 61:1237–1251 [View Article][PubMed]
    [Google Scholar]
  17. Tiffert Y, Supra P, Wurm R, Wohlleben W, Wagner R et al. The Streptomyces coelicolor GlnR regulon: identification of new GlnR targets and evidence for a central role of GlnR in nitrogen metabolism in actinomycetes. Mol Microbiol 2008; 67:861–880 [View Article][PubMed]
    [Google Scholar]
  18. Liao CH, Yao L, Xu Y, Liu WB, Zhou Y et al. Nitrogen regulator GlnR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes. Proc Natl Acad Sci USA 2015; 112:15630–15635 [View Article][PubMed]
    [Google Scholar]
  19. Jenkins VA, Robertson BD, Williams KJ. Aspartate D48 is essential for the GlnR-mediated transcriptional response to nitrogen limitation in Mycobacterium smegmatis. FEMS Microbiol Lett 2012; 330:38–45 [View Article][PubMed]
    [Google Scholar]
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