TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors.
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.
Israël
A
A
Unité de Biologie Moléculaire du Gène, U.277 INSERM, Paris, France.
Le Bail
O
O
Hatat
D
D
Piette
J
J
Kieran
M
M
Logeat
F
F
Wallach
D
D
Fellous
M
M
Kourilsky
P
P
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D016328:NF-kappa B; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP