Epigenetic Mechanisms: Inheritance of Histone States

Epigenetics is a phenomenon important for an overall increase in the complexity of the genome without changes in gene sequence. Epigenetic phenotypes rely on stable inheritance of the binary state of individual gene expression. However, the mechanism of epigenetic inheritance mediated by chromatin is not well characterized, so my proposed research aims to further the understanding of chromatin epigenetics. My working hypothesis is that epigenetic inheritance of gene expression patterns requires the templated, semi- conservative duplication of histone post-translational modifications and of histone variants. In order to experimentally test the existence of templated inheritance of histone modifications and histone variants during the DMAsynthesis phase of the cell cycle, I plan to re-examine the nature of bulk histone inheritance using newly developed tools, including specific antibodies against modified histones and labeled, purified histone complexes. I will also develop a "chromatin replication assay," in which I will test for the existence of gross duplication of particular modifications or variant deposition in an entire genome. Finally, I propose to investigate histone methylation and deacetylation upon and after deposition during DMA replication.