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J. Biol. Chem., Vol. 282, Issue 34, 24767-24776, August 24, 2007

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The Initiator Core Promoter Element Antagonizes Repression of TATA-directed Transcription by Negative Cofactor NC2^*

From the Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom

Core promoter regions of protein-coding genes in metazoan genomes are structurally highly diverse and can contain several distinct core promoter elements, which direct accurate transcription initiation and determine basal promoter strength. Diversity in core promoter structure is an important aspect of transcription regulation in metazoans as it provides a basis for gene-selective function of activators and repressors. The basal activity of TATA box-containing promoters is dramatically enhanced by the initiator element (INR), which can function in concert with the TATA box in a synergistic manner. Here we report that a functional INR provides resistance to NC2 (Dr1/DRAP1), a general repressor of TATA promoters. INR-mediated resistance to NC2 is established during transcription initiation complex assembly and requires TBP-associated factors (TAFs) and TAF- and INR-dependent cofactor activity. Remarkably, the INR appears to stimulate TATA-dependent transcription similar to activators by strongly enhancing recruitment of TFIIA and TFIIB and, at the same time, by compromising NC2 binding.

Received for publication, April 2, 2007 , and in revised form, June 20, 2007.

^* This work was supported in part by a Research Training Network Programme from the European Union (contract no. HPRN-CT-2002-00261), by the Association for International Cancer Research (Grant no. 01-284), and by core funding (to T. O.) provided by Marie Curie Cancer Care. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental data.

¹ Present address: Laboratoire de Biochimie Biologie Moleculaire, EA3922 Estrogenes, Expression Genique et Pathologies du Systeme Nerveux central, IFR 133, Université De Franche-Comte, U.F.R. Sciences et Techniques, 16 Route de Gray, Besancon Cedex, France.

² Present address: EMBL Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.

³ To whom correspondence should be addressed: Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK. Tel.: 44-1883-722306; Fax: 44-1883-714375; E-mail: t.oelgeschlager{at}mcri.ac.uk.

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