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

Joost H.A. Martens, Arie B. Brinkman, Femke Simmer, Kees Jan Francoijs, Angela Nebbioso, Felicetto Ferrara, Lucia Altucci, Hendrik G. Stunnenberg

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

247 Citaten (Scopus)

Samenvatting

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

Originele taal-2Engels
Pagina's (van-tot)173-185
Aantal pagina's13
TijdschriftCancer Cell
Volume17
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - 17 feb. 2010
Extern gepubliceerdJa

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