The human interferon-inducible protein, IFI 16, is a repressor of transcription

R W Johnstone1, J A Kerry, J A Trapani

  • 1The Austin Research Institute, Austin Hospital, Studley Road, Heidelberg 3084, Victoria, Australia. r.johnstone@ari.unimelb.edu.au

Insights

Interferon-inducible protein 16 (IFI 16) acts as a transcriptional repressor. Its repression domains are located in repeat regions common to related proteins, influencing gene transcription.

Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • Interferon-inducible protein 16 (IFI 16) belongs to a family of interferon-inducible proteins with unknown functions.
  • IFI 16 possesses a DNA-binding domain and a nuclear localization signal, suggesting a role in nuclear processes.
  • Previous hypotheses proposed a role for IFI 16 in transcription regulation.

Purpose of the Study:

  • To investigate the molecular function of IFI 16.
  • To determine if IFI 16 can regulate gene transcription.
  • To identify the domains responsible for IFI 16's transcriptional activity.

Main Methods:

  • Fusion of IFI 16 to the GAL4 DNA binding domain to assess transcriptional activity.
  • Reporter gene assays using promoters with GAL4 binding elements.
  • Mapping of repression domains within the IFI 16 protein sequence.
  • Testing IFI 16's effect on the human cytomegalovirus UL54 gene promoter.

Main Results:

  • IFI 16 functions as a transcriptional repressor when fused to the GAL4 DNA binding domain.
  • Repression is independent of binding site position and distance from the transcription start site.
  • Transcriptional repression domains were mapped to conserved 200 amino acid repeat regions.
  • Wild-type IFI 16 repressed transcription from the human cytomegalovirus UL54 promoter.

Conclusions:

  • IFI 16 is a functional transcriptional repressor.
  • The protein exhibits a modular structure characteristic of transcription regulators.
  • The identified repression domains are conserved across human and mouse family members.

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