PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing

Nat Immunol. 2004 Mar;5(3):299-308. doi: 10.1038/ni1046. Epub 2004 Feb 22.

Abstract

PRDI-BF1, the human ortholog of mouse Blimp-1, is a DNA-binding protein involved in postinduction repression of interferon-beta gene transcription in response to viral infection. PRDI-BF1 also has an essential function in driving terminal differentiation of B lymphocytes and therein silences multiple genes. Here we show PRDI-BF1 assembles silent chromatin over the interferon-beta promoter in the osteosarcoma cell line U2OS through recruitment of the histone H3 lysine methyltransferase G9a. G9a is recruited only when in a complex with PRDI-BF1. G9a catalytic activity is required for the accumulation of methylated histone H3 and transcriptional silencing mediated by PRDI-BF1 in vivo. This establishes a mechanism for the recruitment of G9a, the main mammalian euchromatic methyltransferase, and defines nonembryonic targets of G9a.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • Chromatin / genetics
  • Gene Silencing*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase*
  • Humans
  • Interferon-beta / genetics
  • Macromolecular Substances
  • Methyltransferases / metabolism*
  • Molecular Sequence Data
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Methyltransferases
  • Protein Transport
  • Repressor Proteins / physiology*
  • Substrate Specificity
  • Transcription Factors / physiology*
  • Transcription, Genetic

Substances

  • Chromatin
  • Macromolecular Substances
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • Interferon-beta
  • Histone Methyltransferases
  • Methyltransferases
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase