Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation

被引：236

作者：

Chandra, Tamir ^{[1
,2
]}

Kirschner, Kristina ^{[1
]}

Thuret, Jean-Yves ^{[3
]}

Pope, Benjamin D. ^{[4
]}

Ryba, Tyrone ^{[4
]}

Newman, Scott ^{[5
,6
]}

Ahmed, Kashif ^{[7
]}

Samarajiwa, Shamith A. ^{[1
,2
]}

Salama, Rafik ^{[1
]}

Carroll, Thomas ^{[1
]}

Stark, Rory ^{[1
]}

Janky, Rekin's ^{[8
]}

Narita, Masako ^{[1
]}

Xue, Lixiang ^{[1
]}

Chicas, Agustin ^{[9
]}

Nunez, Sabrina ^{[11
]}

Janknecht, Ralf ^{[12
]}

Hayashi-Takanaka, Yoko ^{[13
]}

Wilson, Michael D. ^{[1
,2
,7
]}

Marshall, Aileen ^{[1
,14
]}

Odom, Duncan T. ^{[1
,2
]}

Babu, M. Madan ^{[8
]}

Bazett-Jones, David P. ^{[7
]}

Tavare, Simon ^{[1
,2
]}

Edwards, Paul A. W. ^{[5
,6
]}

Lowe, Scott W. ^{[9
,10
]}

Kimura, Hiroshi ^{[13
]}

Gilbert, David M. ^{[4
]}

Narita, Masashi ^{[1
,2
]}

机构：

[1] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England

[2] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England

[3] CEA, IBiTec S, F-91191 Gif Sur Yvette, France

[4] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA

[5] Univ Cambridge, Dept Pathol, Cambridge CB2 0XZ, England

[6] Univ Cambridge, Hutchison MRC Res Ctr, Cambridge CB2 0XZ, England

[7] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[8] MRC Lab Mol Biol, Cambridge CB2 0QH, England

[9] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA

[10] Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA

[11] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[12] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA

[13] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan

[14] Addenbrookes Hosp, Cambridge Hepatobiliary Unit, Cambridge CB2 2QQ, England

来源：

MOLECULAR CELL | 2012年 / 47卷 / 02期

基金：

英国医学研究理事会; 加拿大健康研究院;

关键词：

DEMETHYLASE JMJD3 CONTRIBUTES; INACTIVE X-CHROMOSOME; CELLULAR SENESCENCE; HUMAN GENOME; FACULTATIVE HETEROCHROMATIN; NUCLEAR-ORGANIZATION; EPIGENETIC CONTROL; H3; METHYLATION; LYSINE; CELLS;

D O I：

10.1016/j.molcel.2012.06.010

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：

The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells, heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of presenescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks, nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.

引用

页码：203 / 214

页数：12

共 49 条

[1] Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging [J].