Turner Lab Profile

Research Focus: Epigenetic Effects of Histone Modifications

The histones of the nucleosome core particle are subject to a variety of post-translational modifications to specific residues, including acetylation of lysines, methylation of lysines and arginines, phosphorylation of serines and threonines, ADP-ribosylation and attachment of small peptides such as ubiquitin and SUMO. These modifications are put in place through the actions of families of enzymes that add or remove the modifying groups. The enzymes often require co-factors (acetyl CoA, NADP etc) and their activities are influenced by a variety of metabolic and environmental variables (eg. short chain fatty acids, nicotinamide). Thus, the pattern of histone modifications on the surface of individual nucleosomes varies in response to metabolic and environmental changes. If histone modifications can exert a direct effect on gene expression, as current evidence suggests, then the nucleosome becomes a sensor through which environmental changes impact on genome function. Further, if such environmental changes are heritable (ie. can be passed on from one cell generation to the next), then we have a mechanism by which external signals can change patterns of gene expression and thereby either direct cells down specific differentiation pathways (ie. as part of the normal differentiation process), or subvert this process. Determining the mechanisms by which histone modifications influence gene expression and whether they have a role in the heritability of gene expression patterns, remain central questions in epigenetic research.