Loss of lamin A function increases chromatin dynamics in the nuclear interior

被引:202
作者
Bronshtein, I. [1 ,2 ,3 ]
Kepten, E. [1 ,2 ]
Kanter, I. [1 ,2 ]
Berezin, S. [1 ,2 ]
Lindner, M. [1 ,2 ]
Redwood, Abena B. [4 ]
Mai, S. [5 ]
Gonzalo, S. [4 ]
Foisner, R. [6 ]
Shav-Tal, Y. [2 ,3 ]
Garini, Y. [1 ,2 ]
机构
[1] Bar Ilan Univ, Dept Phys, IL-5290002 Ramat Gan, Israel
[2] Bar Ilan Univ, Nanotechnol Inst, IL-5290002 Ramat Gan, Israel
[3] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel
[4] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
[5] Univ Manitoba, Manitoba Inst Cell Biol, Dept Physiol & Pathophysiol, Canc Care Manitoba, Winnipeg, MB R3E 0V9, Canada
[6] Med Univ Vienna, Vienna Bioctr VBC, Max F Perutz Labs, A-1030 Vienna, Austria
基金
奥地利科学基金会; 加拿大健康研究院; 欧洲研究理事会; 以色列科学基金会;
关键词
PROTEIN DYNAMICS; ORGANIZATION; GENOME; DIFFUSION;
D O I
10.1038/ncomms9044
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2a, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.
引用
收藏
页数:9
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