PML protein organizes heterochromatin domains where it regulates histone H3.3 deposition by ATRX/DAXX

被引：47

作者：

Delbarre, Erwan ^{[1
]}

Ivanauskiene, Kristina ^{[1
]}

Spirkoski, Jane ^{[1
]}

Shah, Akshay ^{[1
]}

Vekterud, Kristin ^{[1
]}

Moskaug, Jan Oivind ^{[1
]}

Boe, Stig Ove ^{[2
]}

Wong, Lee H. ^{[3
]}

Kuntziger, Thomas ^{[4
]}

Collas, Philippe ^{[1
,5
]}

机构：

[1] Univ Oslo, Inst Basic Med Sci, Dept Mol Med, N-0317 Oslo, Norway

[2] Oslo Univ Hosp, Dept Med Biochem, N-0027 Oslo, Norway

[3] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[4] Univ Oslo, Dept Oral Biol, N-0316 Oslo, Norway

[5] Oslo Univ Hosp, Norwegian Ctr Stem Cell Res, N-0027 Oslo, Norway

来源：

GENOME RESEARCH | 2017年 / 27卷 / 06期

关键词：

PROMYELOCYTIC LEUKEMIA; NUCLEAR-BODIES; RAR-ALPHA; CHROMATIN; ATRX; DAXX; GENE; TRANSCRIPTION; MECHANISM; DYNAMICS;

D O I：

10.1101/gr.215830.116

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：

Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains remains largely undeciphered. We report a role of promyelocytic leukemia (PML) protein in the routing of histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains that we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3. Loss of PML impairs deposition of H3.3 by ATRX and DAXX in PADs but preserves the H3.3 loading function of HIRA in these regions. Our results unveil an unappreciated role of PML in the large-scale organization of chromatin and demonstrate a PML-dependent role of ATRX/DAXX in the deposition of H3.3 in PADs. Our data suggest that H3.3 loading by HIRA and ATRX-dependent H3K27 trimethylation constitute mechanisms ensuring maintenance of heterochromatin when the integrity of these domains is compromised.

引用

页码：913 / 921

页数：9

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