Chromatin structure plays a pivotal role in genetic processes including transcription, replication and repair. Understanding the role of chromatin in these processes is pivotal to understanding the etiology of many diseases including cancers and a wide variety of developmental disorders. Although replication is often proposed to be important for the establishment of specific chromatin structures, this has not been determined directly. Taking advantage of our detailed understanding of replication and silencing in the organism Saccharomyces cerevisae, I will analyze the role of replication in the establishment of silenced chromatin at telomeres. My experiments will entail development of an efficient technique to assess replication timing as well as in vivo analysis of the impact of replication timing and replication initiation site usage on the establishment of a silenced chromatin state. These analyses will expand our appreciation of the parameters that dictate the epigenetic establishment of chromatin structures and should provide a basis for further mechanistic examinations of the assembly of specific chromatin structures.
