How do histones regulate gene expression?

One of the key questions in biology is how genes are switched on and off in a regulated manner. Differences in gene expression patterns drive the process of differentiation from stem cells to fully differentiated organisms. Proper control of gene expression is therefore critical for normal development and altered gene regulation is a hallmark of a number of human diseases, including cancers.

This project will investigate how the chromosomal packaging of DNA by a histone variant, H2A.Z, regulates gene expression. H2A.Z is a specialised variant of H2A that is targeted to specific genomic regions, particularly gene promoters, where it alters the properties of chromatin. The precise roles of H2A.Z in regulating gene expression are unknown. This interdisciplinary project will incorporate both experimental and computational approaches, and the successful applicant will learn a wide range of biochemical, genetic, and genomic techniques, including chromatin immunoprecipitation and next generation sequencing, as well as computational analysis of genomic datasets. Because of the high level of conservation of histones, initial analyses will be carried out using the model organism Saccharomyces cerevisiae but the project may also be extended to mammalian systems. These studies will increase our knowledge of gene regulation by histone variants and will potentially lead to greater understanding of disease states such as cancer.