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J. Biol. Chem., Vol. 277, Issue 52, 50318-50325, December 27, 2002
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-Nucleosome Interactions*
**,
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
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 TIF1
Division of Developmental Genetics, MRC-National
Institute for Medical Research, The Ridgeway, Mill Hill, London NW7
1AA, United Kingdom
, 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
TIF1
-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.
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.
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