Shaping the Epigenome by Histone Protein Exchange and Inheritance
Conference Recording Mar 01, 2014
About the Speaker
Fred van Leeuwen performed his PhD studies on the role of the unusual DNA base J in antigenic variation of African trypanosomes. He performed his post-doctoral training at the Fred Hutchinson Cancer Research Center in Seattle where he identified Dot1 as a methyltransferase of H3K79, a conserved histone modification system on the nucleosome core. In 2004, he started his independent research group as Antoni van Leeuwenhoek Fellow and recently became staff member at the Netherlands Cancer Institute, Amsterdam. His lab currently investigates the function and regulation of Dot1 in yeast and mammals and mechanisms of histone turnover and inheritance.
Abstract Epigenetic mechanisms of gene regulation and transcriptional memory are involved in normal development and disease. Our lab is combining the development of novel assays with genomics and proteomics approaches to unravel mechanisms of epigenetic regulation in budding yeast. Using a ‘genetic pulse-chase assay’ we monitor turnover and inheritance of histone proteins in budding yeast. We find that histones can be dynamic in non-replicating cells and are non-randomly inherited in replicating cells, putting constraints on models for epigenetic memory. Histone exchange and inheritance can influence the epigenome in many ways. To understand the biological significance of histone dynamics we are determining the connections with histone post-translational modifications. In addition, we are developing chromatin barcode screen to discover the genes and mechanisms involved in histone dynamics.