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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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R. E. Collins, M. Tachibana, H. Tamaru, K. M. Smith, D. Jia, X. Zhang, E. U. Selker, Y. Shinkai, and X. Cheng (2005)
J. Biol. Chem. 280, 5563-5570
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FOXC1 Transcriptional Regulatory Activity Is Impaired by PBX1 in a Filamin A-Mediated Manner.
F. B. Berry, M. A. O'Neill, M. Coca-Prados, and M. A. Walter (2005)
Mol. Cell. Biol. 25, 1415-1424
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Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3.
A. M. Lindroth, D. Shultis, Z. Jasencakova, J. Fuchs, L. Johnson, D. Schubert, D. Patnaik, S. Pradhan, J. Goodrich, I. Schubert, et al. (2004)
EMBO J. 23, 4286-4296
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Remodelling chromatin on a global scale: a novel protective function of p53.
S. J. Allison and J. Milner (2004)
Carcinogenesis 25, 1551-1557
   Abstract »    Full Text »    PDF »
Structures of protein domains that create or recognize histone modifications.
M. J. Bottomley (2004)
EMBO Rep. 5, 464-469
   Abstract »    Full Text »    PDF »
Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3.
B. Mateescu, P. England, F. Halgand, M. Yaniv, and C. Muchardt (2004)
EMBO Rep. 5, 490-496
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In Vivo Dynamics of Swi6 in Yeast: Evidence for a Stochastic Model of Heterochromatin.
T. Cheutin, S. A. Gorski, K. M. May, P. B. Singh, and T. Misteli (2004)
Mol. Cell. Biol. 24, 3157-3167
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Cation-{pi} Interactions as Determinants for Binding of the Compatible Solutes Glycine Betaine and Proline Betaine by the Periplasmic Ligand-binding Protein ProX from Escherichia coli.
A. Schiefner, J. Breed, L. Bosser, S. Kneip, J. Gade, G. Holtmann, K. Diederichs, W. Welte, and E. Bremer (2004)
J. Biol. Chem. 279, 5588-5596
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