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EnglishMany 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: | |
| Data di pubblicazione: | 2010 |
| Rivista: | |
| Handle: | http://hdl.handle.net/11591/186611 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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