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

被引：234
|
作者：
Martens, Joost H. A. [1 ]
Brinkman, Arie B. [1 ]
Simmer, Femke [1 ]
Francoijs, Kees-Jan [1 ]
Nebbioso, Angela [2 ]
Ferrara, Felicetto [3 ]
Altucci, Lucia [2 ]
Stunnenberg, Hendrik G. [1 ]
机构：
[1] Radboud Univ Nijmegen, Fac Sci, Nijmegen Ctr Mol Life Sci, Dept Mol Biol, NL-6500 HB Nijmegen, Netherlands
[2] Univ Naples 2, Dipartimento Patol Gen, I-80138 Naples, Italy
[3] Osped Antonio Cardarelli, I-80131 Naples, Italy
来源：
CANCER CELL | 2010年 / 17卷 / 02期
关键词：
ACID-INDUCED DIFFERENTIATION; RETINOIC ACID; HISTONE DEACETYLASE; DNA METHYLATION; CELL-DIFFERENTIATION; GENE-EXPRESSION; FUSION PROTEINS; RXR; COMPLEX; BINDING;
D O I：
10.1016/j.ccr.2009.12.042
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Many different molecular mechanisms have been associated with PML-RAR alpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RAR alpha binding sites in an acute promyelocytic leukemia (APL) cell line and in two APL primary blasts. We found colocalization of PML-RAR alpha 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-RAR alpha/RXR binding sites or at nearby target genes. Our results suggest that PML-RAR alpha/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.
引用
收藏
页码：173 / 185
页数：13
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