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

Martens, Jh; Brinkman, Ab; Simmer, F; Francoijs, Kj; Nebbioso, Angela; Ferrara, F; Altucci, Lucia; Stunnenberg, Hg

doi:10.1016/j.ccr.2009.12.042

Many different molecular mechanisms have been associated with PML-RARa-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARa binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RARa 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-RARa/RXR binding sites or at nearby target genes. Our results suggest that PML-RARa/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.

Titolo:	PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia
Autori:	MARTENS JH BRINKMAN AB SIMMER F FRANCOIJS KJ NEBBIOSO, Angela FERRARA F ALTUCCI, Lucia STUNNENBERG HG mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2010
Rivista:	CANCER CELL
Handle:	http://hdl.handle.net/11591/186611
Appare nelle tipologie:	1.1 Articolo in rivista

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http://hdl.handle.net/11591/186611

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