This report is comprised of two parts: the first is a summary of the teaching and lectures delivered and the second is a research activity report. The topic chosen for my lectures this year, namely chromatin inheritance, is at central to the theme of my chair of Epigenetics and cellular memory. Chromatin is the physiological template of the genome. It serves to package the genome in the nucleus, but it is also a purveyor of information, in addition to the DNA sequence. It acts to integrate signals that enable differential gene expression, DNA replication or repair, but it also acts as a buffer against untimely or inappropriate changes in gene activity. The mechanisms that enable specific chromatin states to be transmitted across cell divisions, or across generations, lie at the heart of epigenetics. The molecular building block of chromatin is the nucleosome – consisting of an octamer of histones around which 146 base pairs of DNA is wrapped. Initially, nucleosomes were regarded as rather inert scaffolds that could be packaged into more open euchromatin or more closed heterochromatin. The discovery that histones can exist in multiple states – different variants, different post-translational modifications as well as the proteins that can associate with them, led to the realisation that chromatin carries a huge potential of information to differentially mark the genome.
Furthermore, it became increasingly clear that far from being inert, chromatin states are highly dynamic. This came as a surprise given the apparently stable states that can be found in some types of heterochromatin and euchromatin. In this series of lectures, I traced the history of chromatin biology, and its different constituents – as well as its diversity of states under different circumstances. I also explored the notion of heritability through the cell cycle and across generations; the mechanisms and timing when memory is challenged: namely during DNA replication when chromatin states must somehow be propagated, as the genome is being copied; and in the germ line, where chromatin states must be erased and then reset in order to prepare for the gametes, that will provide the next generation. Finally I discussed the emerging models for chromatin memory – how different combinations of writers, readers and erasers of histone modifications are balanced to ensure maintenance or reprogramming. This year’s series of lectures form an important basis for many of the topics that I will cover in coming years, including cancer where chromatin memory can be aberrantly lost or acquired, and thus contribute to the gene misregulation that participates in tumorigenesis.