Abstract
BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsWe find that DEK binds to transcription start sites with a dual role in activation and repression of highly and ubiquitously expressed genes.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-215) contains supplementary material, which is available to authorized users.
Highlights
The DEK oncogene is highly expressed in many types of cancers, including breast, ovarian, bladder, colon, and skin cancer as well as acute myeloid leukemia [1,2,3]
The DEK gene is part of the t(6;9) chromosomal translocation resulting in the DEK-NUP214 fusion gene, which is found in 1% of acute myeloid leukemias and promotes cellular proliferation and transformation [10,11]
We find that DEK binds to transcription start sites of highly and ubiquitously transcribed genes and that DEK binding can serve to either promote or repress transcription
Summary
The DEK oncogene is highly expressed in many types of cancers, including breast, ovarian, bladder, colon, and skin cancer as well as acute myeloid leukemia [1,2,3]. The expression is generally high in rapidly proliferating cells and knockdown of DEK by shRNA reduces the proliferation of cell lines from several tissues [1,12]. In HeLa cells, DEK depletion leads to apoptosis through p53 stabilization, whereas knockdown of DEK in melanoma cells causes downregulation of the anti-apoptotic protein MCL-1 [2,17]. DEK is implicated in several essential oncogenic mechanisms, including both proliferation, differentiation and apoptosis. 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
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