Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization

被引：54

作者：

Bosch-Presegue, Laia ^{[1
,2
]}

Raurell-Vila, Helena ^{[1
]}

Thackray, Joshua K. ^{[3
]}

Gonzalez, Jessica ^{[1
]}

Casal, Carmen ^{[4
]}

Kane-Goldsmith, Noriko ^{[3
]}

Vizoso, Miguel ^{[5
]}

Brown, Jeremy P. ^{[6
]}

Gomez, Antonio ^{[7
]}

Ausio, Juan ^{[8
]}

Zimmermann, Timo ^{[9
]}

Esteller, Manel ^{[5
]}

Schotta, Gunnar ^{[10
,11
]}

Singh, Prim B. ^{[6
,12
]}

Serrano, Lourdes ^{[3
]}

Vaquero, Alejandro ^{[1
]}

机构：

[1] Inst Invest Biomed Bellvitge IDIBELL, Canc Epigenet & Biol Program PEBC, Chromatin Biol Lab, Av Gran Via Hospitalet,199-203, Barcelona 08907, Spain

[2] Univ Cent Catalunya, Univ Vic, Dept Biosci, Tissue Repair & Regenerat Grp, Catalunya, Vic, Spain

[3] Rutgers State Univ, Inst Human Genet, Dept Genet, 145 Bevier Rd, Piscataway, NJ 08854 USA

[4] Inst Invest Biomed Bellvitge IDIBELL, Microcopy Unit, Av Gran Via Hospitalet,199-203, Barcelona 08908, Spain

[5] Inst Invest Biomed Bellvitge IDIBELL, Canc Epigenet & Biol Program PEBC, Canc Epigenet Lab, Av Gran Via Hospitalet,199-203, Barcelona 08908, Spain

[6] Charite, Inst Zell & Neurobiol, Facherverbund Anat, D-10117 Berlin, Germany

[7] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain

[8] Univ Victoria, Ctr Biomed Res, Victoria, BC V8W 3N5, Canada

[9] Ctr Genom Regulat, Adv Light Microscopy Unit, C-Dr Aiguader 88, Barcelona 08003, Spain

[10] Ludwig Maximilians Univ Munchen, Martinsried, Germany

[11] Munich Ctr Integrated Prot Sci CiPSM, Biomed Ctr, Planegg Martinsried, Germany

[12] Nazarbayev Univ, Sch Med, Dept Biomed Sci, Astana 010000, Kazakhstan

来源：

CELL REPORTS | 2017年 / 21卷 / 08期

基金：

加拿大健康研究院;

关键词：

HISTONE H3; CHROMATIN COMPACTION; PHASE-SEPARATION; LYSINE; 9; PROTEINS; METHYLATION; MECHANISMS; HP1-ALPHA; DYNAMICS; COHESIN;

D O I：

10.1016/j.celrep.2017.10.092

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1 alpha, HP1 beta, and HP1 gamma play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1 alpha(-/-), Hp1 beta(-/-), and Hp1 gamma(-/-) MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1a confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects. In contrast, HP1b is functionally associated with Suv4-20h2 and H4K20me3, and its loss induces global chromatin decompaction and an abnormal enrichment of CTCF in PCH and other genomic regions. Our work provides insight into the roles of HP1 proteins in heterochromatin structure and genome stability.

引用

页码：2048 / 2057

页数：10

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