Royal Society University Research Fellow,
Division of Structural Biology,
Henry Wellcome Building for Genomic Medicine,
Oxford, OX3 7BN, UK
Telephone: (+44) (0)1865 287560
E-mail: erika@strubi.ox.ac.uk
Our group is interested in the regulation of gene transcription by chromatin remodelling.
All cells in the human body start off with the same set of genes, yet at any point in time and in any particular tissue or organ, only a small subset of the initial pool is "turned on" or transcribed. The process of gene transcription regulation is strongly linked to the physical packaging of the DNA in the eukaryotic cell, the chromatin. The repeating unit of chromatin, the nucleosome, consists of DNA that is wound nearly twice around an octamer of histone proteins (see Figure). The chromatin is continuously packed and unpacked, a process known as chromatin remodelling, which is governed by the chemical modifications encoded in the histone tails and by the physical movement of the nucleosomes.
The importance of chromatin structure in human disease has become increasingly clear as mutations in genes whose products are predicted to regulate chromatin structure often cause complex multi-system diseases and cancer. To understand chromatin remodelling biology it is of crucial importance to unravel the basic structural and functional features of chromatin remodelling ATPases that are at the heart of the remodelling activity. Chromatin remodelling ATPases, characterized by the presence of an ATPase domain and by one or more histone binding domain (chromodomain, PHD domains, bromodomains etc.), are able to alter the histone-DNA interactions within the nucleosomes. Our research efforts are focused on understanding at a molecular level how chromatin remodelling proteins remodel the nucleosome and how the auxiliary histone binding domains participate in the remodelling reaction. To obtain insights into these cellular processes, we use X-ray crystallography in combination with Cryo-EM, NMR, SAXS and a range of biochemical and biophysical techniques.