Investigating the regulation of transcription by a nucleosome remodeling and deacetylation complex

Aims
To discover molecular mechanisms that specify heterochromatin and silence transcription.

Background
Epigenetic mechanisms are essential in establishing the transcriptional programs of eukaryotic cells, which drive cellular identity and are disturbed in many diseases. We focus on understanding mechanisms that silence genomic regions and use the yeast model system S. pombe to establish the relationship between structure and function down to the atomic level. The nucleosome remodelling and deacetylation complex SHREC is a prototype for complexes of this class, the NuRD complexes, that are conserved in animals and plants. We have established structures of the building blocks of the complex and have identified several key interactions that underpin its architecture (Job et al. 2016). Building on our previous work we now want to understand how the complex interacts with its chromatin template and how these interactions contribute to the specific recruitment of the complex to genomic regions for gene silencing.

Approaches
The student will use both biochemical and structural methods (X-ray crystallography, cryo-EM and NMR are available) to purify and structurally characterize the supramolecular complexes. Concomitantly the student will also employ S. pombe genetic methods and perform functional studies to measure silencing and recruitment of heterochromatin factors to specific genomic regions.