Structural characterisation of the tetrasome and histone chaperones

DNA provides the genetic information that defines living organisms. However, at any one time only a proportion of genes are required to be active. An important step in regulating when genes are active is how accessible they are. In this proposal we will investigate the early steps in the packaging of DNA. This is fundamental to understanding how genes are regulated in humans and what goes wrong in a broad range of human diseases.

The genomes of eukaryotes exisist as chromatin. The fundamental subunit of chromatin is the nuclesome. Nucleosomes are dissassembled and reassembled to allow access to genetic infromation for example during DNA replication. An early intermediate in the assembly of nucleosomes is the tetrasome, consisting of histones H3 and H4 associated with DNA. We aim to study the structure of the tetrasome using a range of techniques including SDSL, PELDOR and site directed crosslinking. Histone binding proteins known as histone chaperones are know to facilitate the assembly of tetrasomes. In order to gain insight as to how chaperones achieve this we will investigate how histones are bound by chaperones with the aim of gaining further insight into this important initial step in chromatin assembly.