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