Evolutionary plasticity in the innate immune function of Akirin

PLoS Genet. 2018 Jul 23;14(7):e1007494. doi: 10.1371/journal.pgen.1007494. eCollection 2018 Jul.

Abstract

Eukaryotic gene expression requires the coordinated action of transcription factors, chromatin remodelling complexes and RNA polymerase. The conserved nuclear protein Akirin plays a central role in immune gene expression in insects and mammals, linking the SWI/SNF chromatin-remodelling complex with the transcription factor NFκB. Although nematodes lack NFκB, Akirin is also indispensable for the expression of defence genes in the epidermis of Caenorhabditis elegans following natural fungal infection. Through a combination of reverse genetics and biochemistry, we discovered that in C. elegans Akirin has conserved its role of bridging chromatin-remodellers and transcription factors, but that the identity of its functional partners is different since it forms a physical complex with NuRD proteins and the POU-class transcription factor CEH-18. In addition to providing a substantial step forward in our understanding of innate immune gene regulation in C. elegans, our results give insight into the molecular evolution of lineage-specific signalling pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / immunology*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology*
  • Cell Cycle Proteins / metabolism
  • Chromatin / immunology
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / immunology
  • Evolution, Molecular*
  • Gene Expression Regulation / immunology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Homeodomain Proteins / metabolism
  • Immunity, Innate*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / immunology
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Protein Binding / immunology
  • Transcription Factors / immunology
  • Transcription Factors / metabolism

Substances

  • Akir-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Homeodomain Proteins
  • Transcription Factors
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex