Grant: Catalyst Grant - CEEHRC Epigenetics, Environment & Health

The human genome is made up of equal parts DNA and histone proteins, and it is now recognized that histones play important roles in controlling how genes are expressed. For example, many different chemical tags (marks) can be added (or removed) from histones and specific combinations of these marks form unique signatures that instruct the cell how and when to turn specific genes on or off. The instructions encoded by such epigenetic signatures are read and interpreted by a variety of nuclear proteins that recognize and bind to these chemical tags. Therefore, deciphering the meanings of different epigenetic signatures and identifying the proteins that read these combinations are paramount to understanding how the epigenome works. My lab has developed a new technique whereby we can isolate histones with one specific chemical tag and identify the other tags that work with this particular modification. For example, we first focused on histone H3 phosphorylation and found that phosphorylated H3 is coupled to hyper-acetylated H3 and H4. For this proposal, we are using mass spectrometry to comprehensively identify all histone modifications that are coupled to H3 phosphorylation and this method can identify novel histone marks involved in this pathway. In addition, we are also adapating this method to identify proteins that specifically recognizes the combination of phosphorylated and acetylated histones. Once we have perfected this technique, we will be able to systematically decipher the combinations of epigenetic marks that work together and identify the proteins that interpret these specific signatures.