An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

Each chromosome requires a single centromere and associated kinetochore to ensure its accurate segregation to daughter nuclei. We want to understand how the chromosomal location of centromeres is 'chosen' to direct kinetochore assembly.
This requires a complete appreciation of how two distinct types of centromeric chromatin - heterochromatin and kinetochore-associated CENP-A chromatin – are assembled. Does centromeric DNA have intrinsic properties? Are transcription-coupled events and specific histone modifications involved? We aim to unravel how genetic and epigenetic information converge to define centromere location. We aspire to provide a detailed mechanistic understanding of the sequence of events that culminate in functional centromere-kinetochore formation.

We utilize fission yeast as a model organism. We are sequencing CENP-A nucleosomes in vivo, and assembled in vitro, and developing models to determine if CENP-A nucleosomes have intrinsic DNA sequence preferences relative to H3 nucleosomes. We are also implementing novel affinity selection procedures to understand how neighbouring methyl-H3K9 heterochromatin influences CENP-A chromatin and kinetochore assembly. Communities.

Lab Manager/Assistant: Georgina Hamilton UK