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

被引：238

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

页码：173 / 185

页数：13

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