Grant: Operating Grant

Approximately two metres of DNA is packaged into the nucleus of a single human cell. This event is facilitated by a class of proteins known as histones that, akin to thread on spools, compact the DNA into a compartment that is only 0.00002-0.00004 metres in diameter. Current data suggests that only 5% of the human genome codes for proteins, the basic building blocks of our cells. Storing the remaining 95% of DNA in an inaccessible form is important for both genome stability and for protection of our cells from the dangerous effects of the parasitic retroviral DNA elements that reside within our genomes. Our cells are therefore challenged with the task of keeping 5% of the genome in an active and accessible state, while maintaining the remaining 95% as inactive and inaccessible. This is analogous to playing "Three Card Monte" with twenty cards. The research in my lab strives to understand how our cells "cheat" at Monte by marking the coding regions of our genomes as "active" and protecting these regions from factors that inactivate the remaining parts of the genome. We are specifically interested in understanding the role of a chemical modification of histones, known as acetylation, that our cells use as a molecular flag to label regions of gene expression. Histone acetylation controls gene expression and changes in histone acetylation occur during aging and cancer development. Drugs are currently being developed that can regulate histone acetylation, and in addition to their use as cancer treatments, they are being studied for efficacy in treatment of a wide range of diseases such as Alzheimer's disease, Huntington's disease, Lupus, and rheumatoid arthritis. However despite the applicability these drugs in the treatment of multiple diseases, there remain large gaps in our knowledge regarding the establishment and function of histone acetylation. We study the importance of histone acetylation on gene expression using baker's yeast as a model organism.