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

A Israel, O Le Bail, D Hatat, J Piette, M Kieran… - The EMBO …, 1989 - embopress.org
A Israel, O Le Bail, D Hatat, J Piette, M Kieran, F Logeat, D Wallach, M Fellous, P Kourilsky
The EMBO journal, 1989embopress.org
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 …
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.
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