Higher order chromatin structure determines the functional properties of a distinct chromosomal region. During the last years it became clear that histone modifications represent marks for the specific state of the chromatin structure. In this respect hist one H3 lysine 9 (H3K9) methylation has been shown to be an evolutionary conserved mark for silent chromatin. Suv39h1 and Suv39h2, homologues of Su(var)3-9, one of the strongest suppressors of position-effect variegation in Drosophila, are the major H3K9 me thyltransferases (HMTases) in mouse. Loss-of-function Suv39h mutations result in loss of H3K9 methylation, chromosomal instabilities and increased tumor risk. Genetic screens in Drosophila revealed genes that are involved in the silencing pathway of Su(var )3-9. I will screen for mammalian homologues of those genes and investigate their functions in the mouse system. This approach will result in the identification of novel components involved in the establishment of silent chromatin structures. Analyses of t hese genes in mouse will further reveal their functions in mammalian development and possible pathological implications. To understand the selection of DNA targets for silencing, I will investigate mechanisms that are required for targeting Suv39h enzymes to heterochromatin. I'm very interested in mechanisms of epigenetic gene regulation. After having worked with Drosophila I will acquire experience in using the mouse system, therewith complementing my experimental skills. The tight integration in European and national scientific networks will offer me the opportunity to meet top-level scientists and to develop new concepts and ideas which will help me to finally establish a scientific career as an independent researcher.
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