PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells

被引：58

作者：

Chang, Fiona T. M. ^{[1
]}

McGhie, James D. ^{[1
]}

Chan, F. Lyn ^{[1
]}

Tang, Michelle C. ^{[2
]}

Anderson, Melissa A. ^{[2
]}

Mann, Jeffrey R. ^{[2
]}

Choo, K. H. Andy ^{[2
]}

Wong, Lee H. ^{[1
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[2] Univ Melbourne, Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Paediat, Parkville, Vic 3052, Australia

来源：

NUCLEIC ACIDS RESEARCH | 2013年 / 41卷 / 08期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

PROMYELOCYTIC LEUKEMIA BODIES; NUCLEAR-BODIES; HISTONE CHAPERONE; ATRX; DAXX; PROTEIN; MUTATIONS; LENGTH; H3.3; HETEROCHROMATIN;

D O I：

10.1093/nar/gkt114

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have previously shown that alpha-thalassemia mental retardation X-linked (ATRX) and histone H3.3 are key regulators of telomeric chromatin in mouse embryonic stem cells. The function of ATRX and H3.3 in the maintenance of telomere chromatin integrity is further demonstrated by recent studies that show the strong association of ATRX/H3.3 mutations with alternative lengthening of telomeres in telomerase-negative human cancer cells. Here, we demonstrate that ATRX and H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse ES cells. The assembly of these telomere-associated PML bodies is most prominent at S phase. RNA interference (RNAi)-mediated knockdown of PML expression induces the disassembly of these nuclear bodies and a telomere dysfunction phenotype in mouse ES cells. Loss of function of PML bodies in mouse ES cells also disrupts binding of ATRX/H3.3 and proper establishment of histone methylation pattern at the telomere. Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere.

引用

页码：4447 / 4458

页数：12

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