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Originally published In Press as doi:10.1074/jbc.M203759200 on October 15, 2002

J. Biol. Chem., Vol. 277, Issue 52, 50318-50325, December 27, 2002
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The Bromodomain Mediates Transcriptional Intermediary Factor 1alpha -Nucleosome Interactions*

Eumorphia RemboutsikaDagger **, Ken Yamamoto§, Matthias Harbers, and Marc Schmutz||

From the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, BP 163, F-67404 Illkirch cedex, France and the Dagger  Division of Developmental Genetics, MRC-National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom

Nuclear histone acetyltransferases, DNA-dependent ATPases, and transcriptional intermediary factors (TIFs) all harbor a distinct structural module known as the bromodomain (BrD). Although the BrD can interact with histones H3 and H4 and their acetylated N-terminal tails in vitro, its function in a chromosomal environment remains elusive. We used the nuclear receptor coregulator TIF1alpha , a protein kinase that associates tightly with euchromatin, to analyze the properties of the BrD in a nucleosomal environment in vitro. Here, we report that TIF1alpha -chromatin association is direct and involves DNA and nucleosome interactions mediated by the BrD. Mutation of the BrD signature peptide, PMDL, abolishes DNA binding and disrupts BrD-nucleosome interactions. Based on our results, we propose that the BrD plays a critical role in vivo by directing transregulators to their cognate location on nucleosomal DNA.


* This work was supported in part by grants from CNRS, INSERM, Hopitaux Universitaires de Strasbourg, BMS, and a grant from the Fondation pour la Recherche Médicale.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY155467 and AY155468.

§ Present address: Department of Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.

Supported by E.U. Human Capital and Mobility Fellowship ERBFMBICT941643. Present address: Dnaform International Inc, Tsukuba Branch, 8-3-1 Chuo, Ami Machi, Ibaraki 300-0332, Japan.

|| Present address: Institut Charles Sadron CNRS/ULP, 67083 Strasbourg cedex, France.

** Supported by E.U. Human Capital and Mobility Fellowship ERBCHBGCT940582. To whom correspondence should be addressed at present address: Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, U.K. Tel.: 44-208-816-2169; Fax: 44-208-816-2009; E-mail: erembou@nimr.mrc.ac.uk.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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