Chromatin-based Epigenetic Inheritance. Lessons from the Centromere

The centromere is a unique specialized chromatin domain responsible for driving chromosome segregation. Remarkably, the centromere complex is maintained epigenetically, largely independent of direct in cis DNA sequence information. We are interested in discovering the mechanism of inheritance of non-DNA sequence-based information and use the centromere as a vehicle to do this. Using fluorescent pulse labeling methods we show that the centromeric histone H3 variant CENP-A generates an extremely stable chromatin structure, which is unique to this histone, consistent with providing epigenetic identity to the centromere. Replenishment of new CENP-A is tightly coupled to the cell cycle ensuring synchrony between cell division and centromere propagation. I will present our current efforts to understand how centromeres are established, maintained and fatefully replicated.