Summary
Histones are the fundamental packing material of the genome. Histones and their post-translational modifications play a crucial role in setting up gene expression patterns. During cell division the cell usually faithfully reproduces established patterns of histone modifications when new histones are being deposited into the chromatin. Alterations in histone modifications or mutations in ‘writers’ or ‘readers’ of these epigenetic marks can have profound and long-term effects on gene expression and cell function. As a consequence, epigenetic changes can lead to changes in cell fate and contribute to cancer. While epigenetic changes can mimic genetic changes due to the stability of the epigenetic imprints, they can be reversed by interfering with the enzymes that maintain the post-translational modifications of histone proteins. However, the mechanisms underlying the so called epigenetic memory are still poorly understood. The main goal of this project is to determine how old histone modifications are inherited in dividing cells and how and when new histone modifications are introduced. To address this question, we have developed a novel approach to differentially label old and new histone proteins in the living yeast cell. We will use this novel tool to isolate and analyze old and new histone proteins in replicating cells. In addition, we will determine the stability and residence time of histone proteins in chromosomes. Insight into the mechanisms of inheritance of modified histone proteins will be invaluable to understand the nature of the epigenetic changes that occur in cancer and other diseases.