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Cancer Cell. 2010 Feb 17;17(2):173-85. doi: 10.1016/j.ccr.2009.12.042.

PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia.

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1
Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, the Netherlands.

Abstract

Many different molecular mechanisms have been associated with PML-RARalpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARalpha binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RARalpha with RXR to the vast majority of these binding regions. Genome-wide epigenetic studies revealed that treatment with pharmacological doses of all-trans retinoic acid induces changes in H3 acetylation, but not H3K27me3, H3K9me3, or DNA methylation at the PML-RARalpha/RXR binding sites or at nearby target genes. Our results suggest that PML-RARalpha/RXR functions as a local chromatin modulator and that specific recruitment of histone deacetylase activities to genes important for hematopoietic differentiation, RAR signaling, and epigenetic control is crucial to its transforming potential.

PMID:
20159609
DOI:
10.1016/j.ccr.2009.12.042
[Indexed for MEDLINE]
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