Towards the understanding of the relation between chromatin organization and sub-nuclear pattern of oncoprotein DEK

The DEK oncoprotein is a ubiquitous nuclear factor that has been consistently associated with tumor progression: its expression level differs between normal and cancer cells (1), raising the possibility of using DEK as a tumor marker (2). Moreover, DEK is a non-histone architectural chromatin factor that may influence nucleosomal accessibility and therefore gene activity (3). The interest of this work is to investigate, using super-resolution microscopy approaches, the correlation between the organization of the DEK oncoprotein and the local chromatin structure depending on the degree of cell malignancy. A model based on three well-established human breast cell lines was chosen to represent different subtypes of breast cancer (MCF10A, MCF7 and MDA-MB-231 cells). We performed dual-color confocal and STED imaging followed by the pixel intensity spatial correlation analysis (4), to show the differences of the nanoscale distribution of DEK in relation to the chromatin organization pattern (observed by particular histone modification immunostaining). We expect that this study will provide novel insights into the tumor-promoting activity of DEK and thus progress our understanding of basic mechanisms of cancerogenesis. (1) LM Privette Vinnedge et al., Stacking the DEK: From chromatin topology to cancer stem cells; Cell Cycle; 2013 (2) E Riveiro-Falkenbach and MS Soengas, Control of tumorigenesis and chemoresistance by the DEK oncogene; Clin.Cancer Res.; 2010 (3) C Demeret et al., Chromatin remodelling and DNA replication: from nucleosomes to loop domains; Oncogene; 2001 (4) M Oneto et al., Nanoscale Distribution of Nuclear Sites by Super-Resolved Image Cross-Correlation Spectroscopy; Biophys. J., 201