EPIGENETIC mechanisms - basic research in S. pombe as an experimental model system and epigenetic changes in leukaemia

Epigenetics defines the heritable changes, for example in gene expression, which are not encoded in the DNA itself. Epigenetics refers to the study of single genes or sets of genes whereas epigenomics refers to more global analyses of epigenetic changes across the entire genome. During the last few years our laboratory has established a comprehensive experimental setup for epigenomics in fission yeast (Schizosaccharomyces pombe) as a eukaryotic model organism at the Karolinska Institute in Stockholm. So far the S. pombe experimental setup has been used to study genome-wide roles of some important players in epigenetic regulation. For example, this system was used for a systematic analysis of HDAC enzymes in vivo specificity, HDAC binding maps and expression profiling of HDAC mutants (Wiren, Silverstein et al. 2005) (Durand-Dubief, Sinha et al. 2007) and the genome-wide analysis of CHD group of ATP dependent chromatin remodellers (Walfridsson, Khorosjutina et al. 2007).

Our current research has a focus on questions regarding the role of HDACs, small RNA and chromatin remodellers and histone variants in epigenetic gene regulation. We are also addressing translational aspects of the S. pombe research, in particular regarding HDAC enzymes. Human HDACs play important roles in cancer. We are currently characterizing the histone acetylation changes during normal hematopoiesis and abnormal epigenetic patterns in leukaemia.