Catherine Millar, BA, PhD

Chromatin mediated regulation of gene expression

Chromatin, the mixture of DNA, histones and other proteins that makes up the chromosomes in eukaryotic nuclei, is the physiological substrate for all reactions that center on DNA. Knowledge about chromatin structure and regulation is therefore key to our understanding of gene expression, DNA repair and chromosome replication. My research uses the model organism Saccharomyces cerevisiae to investigate fundamental aspects of chromatin structure and function.

Histone proteins package eukaryotic DNA by forming an octameric complex around which DNA is wound to form nucleosomes. Each nucleosome usually contains two molecules of each of the core histones (H2A, H2B, H3, H4) but in a minority of nucleosomes one of the major histone proteins is replaced by a histone variant. I am interested in the H2A variant H2A.Z, which is a highly conserved protein found in species from yeasts to humans. H2A.Z, like other core histones, is post-translationally modified by acetylation and my research is currently addressing the question of whether H2A.Z acetylation is involved in gene regulation.

It is widely known that DNA contains the instructions for building and running the human body. However, it is less well appreciated that the DNA is tightly packed inside cells by proteins called histones, which restrict access to the DNA sequence. There are a number of different types of histone proteins working together to package DNA, and one of the important roles of histones is to regulate the activity of genes. If gene activity is altered this can lead to a number of developmental disorders or cancers. Research in my lab aims to understand how the histone H2A.Z regulates genes. As H2A.Z is implicated in human cancers, this research will not only increase our understanding of how fundamental cellular processes are regulated but may also help us to understand and treat human diseases in the future.