TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors

EMBO J. 1989 Dec 1;8(12):3793-800. doi: 10.1002/j.1460-2075.1989.tb08556.x.

Abstract

We have dissected the mouse H-2Kb gene promoter in order to define the sequences responsible for induction by tumour necrosis factor (TNF-alpha). An enhancer element (-187 to -158) composed of two imperfect direct palindromic repeats has been shown to be necessary and sufficient for TNF-alpha induction of a heterologous promoter. A multimer of either repeat is also responsive, while a single copy is not: this is the situation in the beta 2-microglobulin (beta 2-m) promoter which contains a single palindrome and does not respond to TNF-alpha. We had previously found that the two repeats can bind a factor named KBF1. We show here that in the uninduced state the transcription factor AP2 binds to the interpalindromic region, while in TNF-treated cells an NF kappa B-like activity is induced which displaces both KBF1 and AP2 and binds to the two palindromes. This strongly suggests that induction of an NF kappa B-like activity is responsible for TNF-alpha stimulation of mouse MHC class I genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cyclic AMP / genetics
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation* / drug effects
  • Genes, MHC Class I*
  • H-2 Antigens / genetics
  • Humans
  • Mice
  • Molecular Sequence Data
  • NF-kappa B
  • Promoter Regions, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Transcription Factor AP-2
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • DNA-Binding Proteins
  • H-2 Antigens
  • NF-kappa B
  • Transcription Factor AP-2
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Cyclic AMP