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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation

Authors: Carl Sandén, Linnea Järvstråt, Andreas Lennartsson, Per Ludvik Brattås, Björn Nilsson, Urban Gullberg

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

The DEK gene is highly expressed in a wide range of cancer cells, and a recurrent translocation partner in acute myeloid leukemia. While DEK has been identified as one of the most abundant proteins in human chromatin, its function and binding properties are not fully understood.

Methods

We performed ChIP-seq analysis in the myeloid cell line U937 and coupled it with epigenetic and gene expression analysis to explore the genome-wide binding pattern of DEK and its role in gene regulation.

Results

We show that DEK preferentially binds to open chromatin, with a low degree of DNA methylation and scarce in the heterochromatin marker H3K9me3 but rich in the euchromatin marks H3K4me2/3, H3K27ac and H3K9ac. More specifically, DEK binding is predominantly located at the transcription start sites of highly transcribed genes and a comparative analysis with previously established transcription factor binding patterns shows a similarity with that of RNA polymerase II. Further bioinformatic analysis demonstrates that DEK mainly binds to genes that are ubiquitously expressed across tissues. The functional significance of DEK binding was demonstrated by knockdown of DEK by shRNA, resulting in both significant upregulation and downregulation of DEK-bound genes.

Conclusions

We find that DEK binds to transcription start sites with a dual role in activation and repression of highly and ubiquitously expressed genes.
Appendix
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Metadata
Title
The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation
Authors
Carl Sandén
Linnea Järvstråt
Andreas Lennartsson
Per Ludvik Brattås
Björn Nilsson
Urban Gullberg
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-215

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