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Linking genome structure with function: A Journey of histone variant discovery

Hosted by: Professor Leonie Quinn

Abstract

My laboratory has shown that the exchange of canonical histones with its variant forms represents one of the most essential alterations to the structure and function of the genome as it is required for early metazoan development, male fertility, chromosome organisation and inheritance, as well as regulating promoter chromatin architecture to maintain or change cell fate. Mechanistically, we have found histone variants perform these crucial functions by directly regulating nucleosome and chromatin stability and accessibility, and indirectly by the recruitment of effector nucleosome binding proteins. My current recent program is aimed at understanding: 1) how the biophysical properties of histone variant-containing nucleosomes regulate the structural transitions from the local ’beads-on-a string’ array of nucleosomes into higher-order chromatin structures fundamental for the three-dimensional organisation of the genome; and 2) how the unique structural and functional properties of histone variants link the epigenome to the establishment and maintenance of cell fate.

Biography

Professor David Tremethick received BSc (Hons) from the University of Sydney and PhD from Macquarie University and CSIRO (Division of Molecular Biology). He was awarded a NIH Fogarty Fellowship and worked as a post-doctoral fellow at the University of Rochester in the US where he developed an in vitro chromatin assembly to study how chromatin contributes to and regulates the gene activation process. Following this, he became a group leader at the JCSMR and for the past 25 years, have focused on understanding the mechanism(s) by which chromatin regulates DNA-dependent processes in order to control cell function and fate. To do this, his laboratory has established many new techniques to study chromatin structure (e.g. establishing the first in vitro chromatin assembly system employing recombinant histones and a range of structural and biophysical approaches), and chromatin function (employing biological systems ranging from Drosophila genetics to Xenopus and mouse development). Over the last decade, David has taken his research to the genome-wide level to study the links between higher-order chromatin structure, the epigenome and the establishment of cell-specific patterns of gene expression.