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Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. There are several pathways, including histone tail mod-ifications, histone variant incorporation, nucleosome remodelling, DNA methylation and noncoding RNAs that together all contribute to the dynamic ‘make-up’ of chromatin under distinct developmental options. | FEBS Journal THE SIR HANS KREBS LECTURE The epigenetic magic of histone lysine methylation Delivered on 6 July 2005 at the 30th FEBS Congress in Budapest Hungary Thomas Jenuwein Research Institute of Molecular Pathology and The Vienna Biocenter Austria Keywords demethylation epigenetic control histone lysine methylation HMTase HP1 binding jumonji histone demethylases mono-di-tri methylstates Suv39h enzymes Correspondence T. Jenuwein Research Institute of Molecular Pathology IMP The Vienna Biocenter Dr. Bohrgasse 7 A-1030 Vienna Austria Fax 43 1 798 7153 Tel 43 1 797 30 474 E-mail jenuwein@imp.univie.ac.at Received 16 March 2006 revised 19 May 2006 accepted 26 May 2006 doi 10.1111 j.1742-4658.2006.05343.x Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. There are several pathways including histone tail modifications histone variant incorporation nucleosome remodelling DNA methylation and noncoding RNAs that together all contribute to the dynamic make-up of chromatin under distinct developmental options. The histone tail modifications are most variable and over 50 marks have by now been mapped. While the majority of these modifications are transient histone lysine methylation and in particular a histone lysine tri-methyl state has been regarded as a more robust signal consistent with proposed roles to impart long-term epigenetic memory. Based on the paradigm of SET-domain histone lysine methyltransferases HMTases and chromo-domain adaptor proteins and in conjunction with the Sir Hans Krebs Medal 2005 I describe here my personal view on the discovery of the first HMTase in 2000 and the subsequent advances on the biology of histone lysine methylation. This discovery has changed my scientific career and significantly contributed to a better understanding of epigenetic control with important implications for heterochromatin formation X inactivation Polycomb group silencing and novel insights into stem cell research nuclear .
