EURODYNA_ The role of linker histone variants and their phosphorylation in chromatin structure an function

The linker histones are known to contribute to the formation and maintenance of higher order chromatin structures but their physiological functions are still largely unknown. They display a complex pattern of variants and recent data suggest that they may have specific roles in epigenetic control of gene expression. The cell cycle dependent phosphorylation of certain serine and threonine residues in the charged tails of the linker histones is most probably of major importance in determining the architecture of chromatin during cell proliferation and differentiation, but the molecular details of this process are very unclear. Aberrant chromatin structure may contribute to malignant transformation and tumour formation. This project aims at elucidating these mechanisms by combining the expertise of Herbert Lindner`s laboratory in Innsbruck and Jean Thomas` laboratory in Cambridge, in collaboration with Ingemar Rundquist`s laboratory in Linköping. All three research groups have many years` experience in linker histone research and the laboratories complement each other well, offering a large range of methods and techniques in analytical chemistry, structural biology, biophysics, and cytochemistry. Together, these investigations should contribute to increased understanding of epigenetic mechanisms involved in chromatin architecture, regulation of cell growth and differentiation, and in malignant transformation and tumour progression.