Evolution of complex histone-based gene regulation

Histones carry a bewildering array of post-translational modifications that affect DNA accessibility, transcription, and splicing. In addition, there are specialized histone variants (e.g. H2A.Z, CENP-A, macroH2A) that can be incorporated into the nucleosome and further affect gene regulation. Alone, but particularly in combination, histone marks and variants can, at least in principle, be used for complex combinatorial control of gene expression. But how did all this mind-boggling complexity evolve? And how did histones become the central platform for eukaryotic gene regulation in the first place? In order to address these questions, we will take advantage of the unique biology of archaea. Many archaeal genomes encode histones, but there are far fewer (1-7) histone variants than in eukaryotes, and those histones are not known to be modified, making archaea a simpler, more tractable system to study incipient complexity. During your PhD you will combine biochemical, evolutionary, genetic and structural approaches to predict and characterize how different archaeal histone paralogs bind DNA, how they interact with each other to form homo- and heteromeric nucleosomes, and how they set up different gene expression states. This project is highly interdisciplinary and the ideal candidate should not only have an interest in evolution and epigenetics but should also be keen to combine computational and experimental work (e.g. biochemistry/structural biology) to learn a wide variety of complementary skills.