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Molecular and Cellular Biology, September 2002, p. 6354-6362, Vol. 22, No. 18
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.18.6354-6362.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-{kappa}B

Elena Ainbinder, Merav Revach, Orit Wolstein, Sandra Moshonov, Noam Diamant, and Rivka Dikstein*

Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel

Received 27 September 2001/ Returned for modification 7 November 2001/ Accepted 9 June 2002

NF-{kappa}B induces the expression of genes involved in immune response, apoptosis, inflammation, and the cell cycle. Certain NF-{kappa}B-responsive genes are activated rapidly after the cell is stimulated by cytokines and other extracellular signals. However, the mechanism by which these genes are activated is not entirely understood. Here we report that even though NF-{kappa}B interacts directly with TAFIIs, induction of NF-{kappa}B by tumor necrosis factor alpha (TNF-{alpha}) does not enhance TFIID recruitment and preinitiation complex formation on some NF-{kappa}B-responsive promoters. These promoters are bound by the transcription apparatus prior to TNF-{alpha} stimulus. Using the immediate-early TNF-{alpha}-responsive gene A20 as a prototype promoter, we found that the constitutive association of the general transcription apparatus is mediated by Sp1 and that this is crucial for rapid transcriptional induction by NF-{kappa}B. In vitro transcription assays confirmed that NF-{kappa}B plays a postinitiation role since it enhances the transcription reinitiation rate whereas Sp1 is required for the initiation step. Thus, the consecutive effects of Sp1 and NF-{kappa}B on the transcription process underlie the mechanism of their synergy and allow rapid transcriptional induction in response to cytokines.

* Corresponding author. Mailing address: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-934 2117. Fax: 972-8-934 4118. E-mail: rivka.dikstein{at}weizmann.ac.il.

Molecular and Cellular Biology, September 2002, p. 6354-6362, Vol. 22, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.18.6354-6362.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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