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Molecular and Cellular Biology, April 2005, p. 2632-2643, Vol. 25, No. 7
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.7.2632-2643.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

TATA-Binding Protein (TBP)-Like Factor (TLF) Is a Functional Regulator of Transcription: Reciprocal Regulation of the Neurofibromatosis Type 1 and c-fos Genes by TLF/TRF2 and TBP

Jayhong A. Chong,^1, Magdalene M. Moran,^2,3, Martin Teichmann,^4, J. Stefan Kaczmarek,^1,5 Robert Roeder,⁴ and David E. Clapham^1,2,3,5*

Department of Cardiology, Children’s Hospital,¹ Department of Neurobiology and,² Program in Neuroscience, Harvard University, and,³ Howard Hughes Medical Institute, Boston, Massachusetts,⁵ Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York⁴

Received 3 August 2004/ Returned for modification 20 September 2004/ Accepted 27 December 2004

The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.

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* Corresponding author. Mailing address: Children's Hospital, Enders 1309, 320 Longwood Ave., Boston, MA 02115. Phone: (617) 355-6163. Fax: (617) 731-0787. E-mail: dclapham{at}enders.tch.harvard.edu.

J.A.C. and M.M.M. contributed equally to this work.

Present address: Institut Européen de Chimie et Biologie, Université Bordeaux 2, 2 Rue Robert Escarpit, 3607 Pessac, France.

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Molecular and Cellular Biology, April 2005, p. 2632-2643, Vol. 25, No. 7
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.7.2632-2643.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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