Abstract

Shaping the Epigenome by Chromatin Dynamics

Fred van Leeuwen, Group Leader, Netherlands Cancer Institute

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.