Robert H. Blelloch, M.D., Ph.D.

Research

I am interested in the dynamics of chromatin structure and its function in the regulation of eukaryotic genes. Among the many features that distinguish eukaryotic cells from their prokaryotic relatives is the nucleosome core particle, the basic building block of chromatin structure. We don’t know yet to what extent the DNA has to be unwrapped at the regulatory sequences of genes to allow for the initiation of transcription. An understanding of the particular mechanisms of eukaryotic gene regulation hinges upon our answers to this question. We study the problem in the unicellular yeast Saccharomyces cerevisiae for the relative simplicity of its promoter structures, its amenability to genetic manipulation and the small size of its genome, which offers many experimental advantages. Using this experimental system we were able to provide evidence for the removal of promoter nucleosomes by complete disassembly of the nucleosome core particle. We have also shown that nucleosome removal is incomplete in a population of cells. Taken together, these observations suggest that a dynamic structural equilibrium between nucleosome disassembly and reassembly lies at the heart of promoter activation at some, if not all, eukaryotic promoters. On-going work in our lab is aimed at testing this hypothesis.