Functions of Histone Modifications and Specific Binding Proteins

Michigan State University, East Lansing MI

Investigators

Abstract

DNA is wrapped around histone proteins within the nuclei of non-bacterial organisms. Histone modifications are linked to a variety of nuclear activities. The molecular mechanisms by which histone modifications function remain largely unknown. In this work, a novel method was developed which allows the identification of protein-protein interactions involving protein modifications, including acetylation. Using this method, several novel acetylated histone binding proteins were identified, implicated in a variety of functions, including chromatin assembly, transcriptional regulation, meiotic recombination, histone methylation, DNA damage repair, and mRNA metabolism. These results suggest that the individual molecular functions of histone acetylation may be unveiled by the studies of their interacting proteins. Given that histones contain more than 30 acetylatable lysines, it is tempting to speculate that many more chromatin functions are exerted via recruiting specific interacting proteins for differently acetylated histones. In this project, an array of acetylated histones for screening will first be created such that different binding proteins that respond to the corresponding acetylation events can be identified. Further functional analyses of such proteins will help reveal the molecular functions of histone acetylation at a global scale. Furthermore, chromatin functions are dynamically regulated via multiple modifications including acetylation, methylation, phosphorylation, and ubiquitination. An increasing number of reports also demonstrates the interplay between different histone modifications. The current studies will provide both technical and intellectual framework for studies of these other histone modifications.