Molecular function of the DEK oncoprotein in global chromatin integrity

• Applicant: Dr. Ferdinand Kappes
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 227390135

Proper maintenance of chromatin integrity is vital to genomic stability, and deregulation thereof might result in the pathogenesis of human diseases, including cancer.Very recently, we have identified the DEK oncogene, a unique and abundant non-histone chromosmal factor with previously enigmatic cellular functions, to be vital to global chromatin integrity in mammalian cells and in Drosophila. Interference with DEK expression leads to alterations of the epigenome due to, at least in part, inefficient or aberrant targeting of Heterochromatin Protein 1 to the repressive histone mark H3K9Me3 (histone H3 tri-methylated at lysine 9). As DEK is frequently found overexpressed in a substantial number of neoplasms, and plays a key role in central pathways of tumor biology, this finding may define a crucial mechanism of how DEK influences gene regulation, DNA repair, and genomic integrity. This project aims at detailing the DEK-HP1 interplay at a biochemical level, on the cellular level, and in the model organism Drosophila. The outcome of these studies is expected to deepen our understanding of the fundamental biological functions of DEK, paving the way for potential therapies that target this unique oncoprotein.

• DFG Programme: Research Grants