Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

Chromo domain of Drosophila HP1 interacts specifically with the N-terminal tail of histone H3 methylated at Lysine 9

Distinct patterns of covalent post-translational modifications within histone tails can influence higher order chromatin structure and epigenetic gene regulation. Recent literature suggests that this regulation may stem from specific proteins or protein modules which bind to uniquely modified histone tails. HP1 (heterochromatin-associated protein 1) is a chromo (chromatin organization modifiers) domain containing protein which has been shown to have dosage-dependant effects on heterochromatin induced gene silencing. Chromo domains are evolutionarily conserved protein domains found in numerous chromatin associated proteins. Here we report that Drosophila HP1 interacts in a specific manner with the N-terminal tail of histone H3 that is methylated at lysine 9, and this interaction is mediated through its chromo domain. Antibodies specific for H3 methylated at lysine 9, demonstrate that HP1 and methylated H3 co-localize in vivo. Analysis of this interaction by NMR shows that, upon titration of methylated histone H3 peptide, a number of residues in 15N labeled chromo domain experience large chemical shift perturbations. The residues that have the largest chemical shift changes are predominantly located near an evolutionarily conserved hydrophobic groove, suggesting that this groove is the site of histone H3 binding. These results suggest that methylation of lysine 9 of histone H3 and its interaction with HP1 play an important role in regulation of heterochomatin-related gene silencing.

Steven A. Jacobs*, Sean D. Taverna*, Yinong Zhang, Jinmei Li, C. David Allis, & Sepideh Khorasanizadeh

Department of Biochemistry and Molecular Genetics, University of Virginia Health Science Center, Charlottesville, VA 22908, USA
Email: saj4r@cms.mail.virginia.edu
*These authors contributed equally to this work