Chromatin Structure and Function

The compaction of DNA into chromatin (the complex of histones and DNA in the nucleus) presents a barrier to processes such as transcription, replication, repair and recombination, since these processes rely on the binding of proteins to packaged DNA recognition sequences. It has also become clear in recent years that an understanding of the varied ensemble of chromatin structures that exist in the nucleus is crucial to understand epigenetic processes and therefore a wide range of diseases ranging from cancer to autism. Linker histones (H1s) play a role in chromatin compaction by facilitating the formation of the 30 nm chromatin fibre. They consist of a central globular domain, flanked by intrinsically unstructured N- and C-terminal domains. While the roles of the globular and C-terminal domains are well established, the function of the N-terminal domain in chromatin remains elusive. We study the secondary structures and DNA- and chromatin-binding properties of the varied N-terminal domains of several H1 isotypes. Continued investigation will allow us to establish structure-function relationships for the N-terminal domains of H1 and will also shed light on the structural barriers that face proteins that need to gain access to DNA. This information is crucial to a fundamental understanding of all nuclear processes and epigenetic diseases