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Fig.2.E showing Immunocytochemistry-immunofluorescence from the publication: DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

Fig.2.D showing Western Blotting from the publication: DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

Fig.3.D showing Western Blotting from the publication: DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

Fig.6.D showing Western Blotting in a Homo sapiens (Human) sample from the publication: SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability.

Fig.6.E showing Western Blotting in a Homo sapiens (Human) sample from the publication: SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability.

Fig.4.B showing Western Blotting in a Homo sapiens (Human) sample from the publication: DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.

Fig.2.A showing Western Blotting from the publication: DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.

Fig.4.A showing Immunohistochemistry from the publication: DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.

Fig.5.E showing Western Blotting from the publication: Regulation of p53 and Rb links the alternative NF-κB pathway to EZH2 expression and cell senescence.

9 images found

DEK promotes mammary hyperplasia and is associated with H3K27me3 epigenetic modifications.

In Life Science Alliance on 1 September 2025 by Johnstone, M. E., Leck, A. L., et al.

The DEK chromatin remodeling protein has oncogenic functions in breast cancers, but its functional role in normal mammary gland epithelium has remained unexplored. We developed two novel genetically engineered mouse models to study the role of Dek in normal mammary gland biology in vivo. Mammary gland-specific Dek transgenic mice developed hyperplasia and had a transcriptional profile that revealed increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited mammary gland functional defects resulting in dramatically reduced pup survival. Analysis of previously published scRNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, up-regulating the levels of histone H3K27me3 to control gene transcription. Combined, this is the first report to show that Dek promotes proliferation of mammary epithelial cells via transcriptional deregulation of cell cycle genes, potentially via epigenetic mechanisms, in vivo.
© 2025 Johnstone et al.

Structural insights into how DEK nucleosome binding facilitates H3K27 trimethylation in chromatin.

In Nature Structural Molecular Biology on 21 February 2025 by Kujirai, T., Echigoya, K., et al.

Structural diversity of the nucleosome affects chromatin conformations and regulates eukaryotic genome functions. Here we identify DEK, whose function is unknown, as a nucleosome-binding protein. In embryonic neural progenitor cells, DEK colocalizes with H3 K27 trimethylation (H3K27me3), the facultative heterochromatin mark. DEK stimulates the methyltransferase activity of Polycomb repressive complex 2 (PRC2), which is responsible for H3K27me3 deposition in vitro. Cryo-electron microscopy structures of the DEK-nucleosome complexes reveal that DEK binds the nucleosome by its tripartite DNA-binding mode on the dyad and linker DNAs and interacts with the nucleosomal acidic patch by its newly identified histone-binding region. The DEK-nucleosome interaction mediates linker DNA reorientation and induces chromatin compaction, which may facilitate PRC2 activation. These findings provide mechanistic insights into chromatin structure-mediated gene regulation by DEK.
© 2025. The Author(s).

DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

In Blood Cancer Journal on 9 October 2024 by Hopper, M. A., Dropik, A. R., et al.

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration. To interrogate the mechanistic role of DEK in B-cell lymphoma, we generated a DEK knockout cell line model, which demonstrated DEK depletion caused reduced proliferation and altered expression of key cell cycle and apoptosis-related proteins, including Bcl-2, Bcl-xL, and p53. Notably, DEK depleted cells showed increased sensitivity to apoptosis-inducing agents, including venetoclax and staurosporine, which underscores the therapeutic potential of targeting DEK in B-cell lymphomas. Overall, our study contributes to a better understanding of DEK's role as an oncoprotein in B-cell lymphomas, highlighting its potential as both a promising therapeutic target and a novel biomarker for aggressive LGBCL. Further research elucidating the molecular mechanisms underlying DEK-mediated tumorigenesis could pave the way for improved treatment strategies and better clinical outcomes for patients with B-cell lymphoma.
© 2024. The Author(s).

The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications

Preprint on BioRxiv : the Preprint Server for Biology on 10 September 2024 by Johnstone, M., Leck, A., et al.

The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells using in vitro and knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biology in vivo . Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.

Association of DDX5/p68 protein with the upstream erythroid enhancer element (EHS1) of the gene encoding the KLF1 transcription factor.

In The Journal of Biological Chemistry on 1 December 2023 by Chen, X., Pillay, S., et al.

EKLF/KLF1 is an essential transcription factor that plays a global role in erythroid transcriptional activation. Regulation of KLF1 is of interest, as it displays a highly restricted expression pattern, limited to erythroid cells and its progenitors. Here we use biochemical affinity purification to identify the DDX5/p68 protein as an activator of KLF1 by virtue of its interaction with the erythroid-specific DNAse hypersensitive site upstream enhancer element (EHS1). We further show that this protein associates with DEK and CTCF. We postulate that the range of interactions of DDX5/p68 with these and other proteins known to interact with this element render it part of the enhanseosome complex critical for optimal expression of KLF1 and enables the formation of a proper chromatin configuration at the Klf1 locus. These individual interactions provide quantitative contributions that, in sum, establish the high-level activity of the Klf1 promoter and suggest they can be selectively manipulated for clinical benefit.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

In Blood Cancer J on 9 October 2024 by Hopper, M. A., Dropik, A. R., et al.

Fig.3.D

DEK depletion inhibits proliferation and is accompanied by reduced expression of cell cycle genes, reduced Bcl-2 and Bcl-xL expression, and increased p53 expression.A Chronos Gene Effect from RNAi of DEK in B-cell lymphoma cell lines. Gene effect represents the impact of DEK RNAi on cellular fitness, with negative values representing a negative impact to cellular fitness. B Validation of DEK knockout by western blot and Sanger sequencing. C In vitro five-day proliferation assay of synchronized SUDHL6 WT versus DEK KO cells. Proliferation was measured by MTT assay with n = 3 biological replicates. Assays were run with technical triplicates. D Western blot analysis of cell cycle, apoptosis, and stress response proteins in SUDHL6 WT and DEK KO cells. Cell lines were harvested at ≥ 95% viability. Blots have been cropped to display indicated proteins based on molecular weight. The corresponding DEK and β-actin controls were processed in parallel and are displayed below their corresponding samples. E Quantifications of protein expression in DEK KO versus WT cells of n = 3 biological replicates. All quantifications were scaled to β-actin levels and fold-changes of DEK KO versus WT were used as input for statistical analysis. Plots depict the mean and SD of log2 fold change values, where negative values represent reduced expression in DEK KO. Blue bars indicate a statistically significant decrease of expression in DEK KO cells, red bars indicate a statistically significant increase in DEK KO cells. less

Collected and cropped from Blood Cancer J by CiteAb, provided under a CC-BY license

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Regulation of p53 and Rb links the alternative NF-κB pathway to EZH2 expression and cell senescence.

In PLoS Genet on 1 September 2014 by Iannetti, A., Ledoux, A. C., et al.

Fig.5.E

EZH2 is a critical effector of an antagonistic cross-talk between NF-κB and p53.(A) Heatmap showing effects on gene expression of NHD fibroblasts depleted for EZH2, NF-κB2, RelB and p53. NHD fibroblasts were transfected in triplicate with the listed siRNAs. After 48 hours RNA was extracted for microarray analysis. Shown with a bar is the group of genes where EZH2, NF-κB2 and RelB antagonize p53 dependent gene expression. (B) A subset of genes is co-regulated by NF-κB2, RelB, EZH2 and p53 in NHD fibroblasts. (C) Graphical representation of the 975 p53 regulated genes whose expression changes >1.5 fold that are also regulated (>1.5×) by NF-κB2, RelB and Ezh2. (D–E) NF-κB2, RelB, EZH2 regulate DEK expression in NHD fibroblasts. RNA (D) and whole cell protein lysates (E) was prepared from NHD fibroblasts treated with the indicated siRNAs and Q-PCR or western blot analysis of DEK expression was performed. Note that (E) is a reprobing of blots used in Fig. 1C and the β-actin blot shown here is the same as in that figure. (F) siRNA mediated knock down of DEK induces cellular senescence. NHD fibroblasts were transfected with the siRNAs shown and analyzed for senescence after 7 days. (G) EZH2 and DEK alone can rescue senescence. Fibroblasts conditionally immortalized with temperature sensitive T antigen (described in Rovillain et al.) were shifted to the non-permissive temperature and subjected to a clonogenic assay with and without expression of the indicated genes. The panel shows an image of cells upon completion of the assay. less

Collected and cropped from PLoS Genet by CiteAb, provided under a CC-BY license

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