This proposal involves a set of studies into the structure and mechanism of interactions between chromo (chromosome organization modifier) domains and histone tails. It is now believed that histone tails, which protrude from the nucleosome particles, play a fundamental role in gene regulation through their capacity for acetylation, methylation and phosphorylation. These histone modifications provide a recognition code that extends the information in the genetic code, and dictates the transition between transcriptionally active and transcriptionally silent chromatin states. We propose to characterize the structural basis of histone code recognition by using NMR spectroscopy and X-ray crystallography to study the interactions between chromo domains of the proteins HP1 (Heterochromatin-associated Protein-1), Esa1 (Essential sas2-related acetyltransferase 1), CDY (Chromo Domain on Y chromosome) and CDYL (CDY-Like) with histone tails. Our preliminary data show that their chromo domains interact with chromatin by directly binding to histone H3 tails. Binding of HP1 and CDY to the H3 tail requires the methylation of lysine 9 (methyl-Lys9) while Esa1 prefers binding to the unmodified H3 tail. Through these studies we hope to reveal the mechanism of histone tail recognition within the family of chromo domain containing proteins.
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| Zhang, Xiaoyu; Germann, Sophie; Blus, Bartlomiej J et al. (2007) The Arabidopsis LHP1 protein colocalizes with histone H3 Lys27 trimethylation. Nat Struct Mol Biol 14:869-71 |
| Hughes, Robert M; Wiggins, Kimberly R; Khorasanizadeh, Sepideh et al. (2007) Recognition of trimethyllysine by a chromodomain is not driven by the hydrophobic effect. Proc Natl Acad Sci U S A 104:11184-8 |
| Lindroth, Anders M; Shultis, David; Jasencakova, Zuzana et al. (2004) Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. EMBO J 23:4286-96 |
