Chromatin Redistribution of the DEK Oncoprotein Represses hTERT Transcription in Leukemias
Abstract
Although numerous factors have been found to modulate hTERT transcription, the mechanism of its repression in certain leukemias remains unknown. We show here that DEK represses hTERT transcription through its enrichment on the hTERT promoter in cells from chronic and acute myeloid leukemias, chronic lymphocytic leukemia, but not acute lymphocytic leukemias where hTERT is overexpressed. We isolated DEK from the hTERT promoter incubated with nuclear extracts derived from fresh acute myelogenous leukemia (AML) cells and from cells expressing Tax, an hTERT repressor encoded by the human T cell leukemia virus type 1. In addition to the recruitment of DEK, the displacement of two potent known hTERT transactivators from the hTERT promoter characterized both AML cells and Tax-expressing cells. Reporter and chromatin immunoprecipitation assays permitted to map the region that supports the repressive effect of DEK on hTERT transcription, which was proportionate to the level of DEK-promoter association but not with the level of DEK expression. Besides hTERT repression, this context of chromatin redistribution of DEK was found to govern about 40% of overall transcriptional modifications, including those of cancer-prone genes. In conclusion, DEK emerges as an hTERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis.
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BibTeX
@article{karam2026chromatin,
title = {{Chromatin Redistribution of the DEK Oncoprotein Represses hTERT Transcription in Leukemias}},
author = {Maroun Karam and Morgan Thenoz and Valérie Capraro and Jean-Philippe Robin and Christiane Pinatel and Agnès Lançon and Perrine Galia and David Sibon and Xavier Thomas and Sophie Ducastelle-Lepretre and Franck Nicolini and Mohamed El-Hamri and Youcef Chelghoun and Eric Wattel and Franck Mortreux},
journal = {Neoplasia},
year = {2026},
month = oct,
doi = {10.1593/neo.131658},
url = {https://hal.science/hal-05795543v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Chromatin Redistribution of the DEK Oncoprotein Represses hTERT Transcription in Leukemias
AU - Maroun Karam
AU - Morgan Thenoz
AU - Valérie Capraro
AU - Jean-Philippe Robin
AU - Christiane Pinatel
AU - Agnès Lançon
AU - Perrine Galia
AU - David Sibon
AU - Xavier Thomas
AU - Sophie Ducastelle-Lepretre
AU - Franck Nicolini
AU - Mohamed El-Hamri
AU - Youcef Chelghoun
AU - Eric Wattel
AU - Franck Mortreux
PY - 2026
DA - 2026/10/12
JO - Neoplasia
DO - 10.1593/neo.131658
UR - https://hal.science/hal-05795543v1
AB - Although numerous factors have been found to modulate hTERT transcription, the mechanism of its repression in certain leukemias remains unknown. We show here that DEK represses hTERT transcription through its enrichment on the hTERT promoter in cells from chronic and acute myeloid leukemias, chronic lymphocytic leukemia, but not acute lymphocytic leukemias where hTERT is overexpressed. We isolated DEK from the hTERT promoter incubated with nuclear extracts derived from fresh acute myelogenous leukemia (AML) cells and from cells expressing Tax, an hTERT repressor encoded by the human T cell leukemia virus type 1. In addition to the recruitment of DEK, the displacement of two potent known hTERT transactivators from the hTERT promoter characterized both AML cells and Tax-expressing cells. Reporter and chromatin immunoprecipitation assays permitted to map the region that supports the repressive effect of DEK on hTERT transcription, which was proportionate to the level of DEK-promoter association but not with the level of DEK expression. Besides hTERT repression, this context of chromatin redistribution of DEK was found to govern about 40% of overall transcriptional modifications, including those of cancer-prone genes. In conclusion, DEK emerges as an hTERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis.
SN - 1522-8002
SN - 1476-5586
ER -