DMMC Course: UNRAVELLING CHROMATIN & THE ROLE OF EPIGENETICS IN DISEASE

1700-1800 Tuesday 25 April 2006. UCD Conway Institute Lecture Theatre

Keynote Lecture: Epigenetic control by histone methylation
Prof Thomas Jenuwein, Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Jenuwein Group

Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. DNA methylation, histone modifications and variants, nucleosome remodelling and non-coding RNAs all contribute to the dynamic 'make-up' of chromatin under distinct developmental options. In particular, the great diversity of covalent histone tail modifications has been proposed to be ideally suited for imparting epigenetic information. While most of the histone tail modifications represent transient marks at transcriptionally permissive chromatin, some modifications appear more robust at silent chromatin regions where they index repressive epigenetic states with functions also outside transcriptional regulation. Under-representation of repressive histone marks could be indicative of epigenetic plasticity in stem, young and tumor cells, while committed and senescent (old) cells often display increased levels of these more stable modifications. We analyzed profiles of normal and aberrant histone lysine methylation patterns, as they occur during the transition of an embryonic to a differentiated cell or in controlled self-renewal vs. pro-neoplastic or metastatic conditions. Elucidating these histone modification patterns promises to have important implications for novel advances in stem cell research, nuclear reprogramming and cancer, and may offer novel targets for the combat of tumor cells, potentially leading to new diagnostic and therapeutic avenues in human biology and disease.