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Science 295 (5562): 2080-2083

Copyright © 2002 by the American Association for the Advancement of Science

Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail

Steven A. Jacobs, Sepideh Khorasanizadeh*

The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a beta  strand, completing the beta -sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain. Comparison of dimethyl- and trimethyllysine-containing complexes suggests a role for cation-pi and van der Waals interactions, with trimethylation slightly improving the binding affinity.

Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908-0733, USA.
*   To whom correspondence should be addressed. E-mail: khorasan{at}virginia.edu

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Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27.
J. Min, Y. Zhang, and R.-M. Xu (2003)
Genes & Dev. 17, 1823-1828
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Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains.
W. Fischle, Y. Wang, S. A. Jacobs, Y. Kim, C. D. Allis, and S. Khorasanizadeh (2003)
Genes & Dev. 17, 1870-1881
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Identification and Characterization of Three New Components of the mSin3A Corepressor Complex.
T. C. Fleischer, U. J. Yun, and D. E. Ayer (2003)
Mol. Cell. Biol. 23, 3456-3467
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Effects of tethering HP1 to euchromatic regions of the Drosophila genome.
Y. Li, J. R. Danzer, P. Alvarez, A. S. Belmont, and L. L. Wallrath (2003)
Development 130, 1817-1824
   Abstract »    Full Text »    PDF »
Assembly of Cell Regulatory Systems Through Protein Interaction Domains.
T. Pawson and P. Nash (2003)
Science 300, 445-452
   Abstract »    Full Text »    PDF »
Does heterochromatin protein 1 always follow code?.
Y. Li, D. A. Kirschmann, and L. L. Wallrath (2002)
PNAS 99, 16462-16469
   Abstract »    Full Text »    PDF »
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing.
R. Cao, L. Wang, H. Wang, L. Xia, H. Erdjument-Bromage, P. Tempst, R. S. Jones, and Y. Zhang (2002)
Science 298, 1039-1043
   Abstract »    Full Text »    PDF »

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