Evolution of the Ikaros family transcription factors: From a deuterostome ancestor to humans.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Ikaros Transcription Factor*/genetics ; Ikaros Transcription Factor*/metabolism ; Zinc Fingers*/genetics; Animals ; Humans ; DNA ; RNA, Messenger
    • Abstract:
      Ikaros family proteins (Ikaros, Helios, Aiolos, Eos) are zinc finger transcription factors essential for the development and function of the adaptive immune system. They also control developmental events in neurons and other cell types, suggesting that they possess crucial functions across disparate cell types. These functions are likely shared among the organisms in which these factors exist, and it is thus important to obtain a view of their distribution and conservation across organisms. How this family evolved remains poorly understood. Here we mined protein, mRNA and DNA databases to identify proteins with DNA-binding domains homologous to that of Ikaros. We show that Ikaros-related proteins exist in organisms from all four deuterostome phyla (chordates, echinoderms, hemichordates, xenacoelomorpha), but not in more distant groups. While most non-vertebrates have a single family member, this family grew to six members in the acoel worm Hofstenia miamia, three in jawless and four in jawed vertebrates. Most residues involved in DNA contact from zinc fingers 2 to 4 were identical across the Ikaros family, suggesting conserved mechanisms for target sequence recognition. Further, we identified a novel KRKxxxPxK/R motif that inhibits DNA binding in vitro which was conserved across the deuterostome phyla. We also identified a EψψxxxψM(D/E)QAIxxAIxYLGA(D/E)xL motif conserved among human Ikaros, Aiolos, Helios and subsets of chordate proteins, and motifs that are specific to subsets of vertebrate family members. Some of these motifs are targets of mutations in human patients. Finally we show that the atypical family member Pegasus emerged only in vertebrates, which is consistent with its function in bone. Our data provide a novel evolutionary perspective for Ikaros family proteins and suggest that they have conserved regulatory functions across deuterostomes.
      Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interest.
      (Copyright © 2023. Published by Elsevier Inc.)
    • Contributed Indexing:
      Keywords: DNA-Binding domain; Deuterostome; Evolution; Ikaros family; Protein motifs
    • Accession Number:
      9007-49-2 (DNA)
      148971-36-2 (Ikaros Transcription Factor)
      0 (RNA, Messenger)
    • Publication Date:
      Date Created: 20231222 Date Completed: 20240127 Latest Revision: 20240909
    • Publication Date:
      20240909
    • Accession Number:
      10.1016/j.bbrc.2023.149399
    • Accession Number:
      38134477