The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity

Ferdinand Kappes; Tanja Waldmann; Veena Mathew; Jindan Yu; Ling Zhang; Michael S. Khodadoust; Arul M. Chinnaiyan; Karolin Luger; Sylvia Erhardt; Robert Schneider; David M. Markovitz

doi:10.1101/gad.2036411

The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity

¹Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA;
²Max-Planck-Institute for Immunobiology, 79108 Freiburg, Germany;
³CellNetworks-Cluster of Excellence, ZMBH-DKFZ-Alliance, ZMBH, Heidelberg University, Heidelberg 69120, Germany;
⁴Department of Pathology, Michigan Center for Translational Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA;
⁵Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Colorado State University, Fort Collins, Colorado 80523, USA;
⁶Program in Immunology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA;
⁷Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA

↵8 These authors contributed equally to this work.
↵9 These authors contributed equally to this work.

↵10 Present addresses: Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany;
↵11 University of Konstanz, Universitätsstr. 10, 78464 Konstanz, Germany;
↵12 Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.

Abstract

Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 α (HP1α) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions. Loss of Dek in Drosophila leads to a Su(var) phenotype and global reduction in heterochromatin. Thus, these findings show that DEK is a key factor in maintaining the balance between heterochromatin and euchromatin in vivo.