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

I. Bronshtein; E. Kepten; I. Kanter; S. Berezin; M. Lindner; Abena B. Redwood; S. Mai; S. Gonzalo; R. Foisner; Y. Shav-Tal; Y. Garini

doi:10.1038/ncomms9044

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

I. Bronshtein, E. Kepten, I. Kanter, S. Berezin, M. Lindner, Abena B. Redwood, S. Mai, S. Gonzalo, R. Foisner, Y. Shav-Tal, Y. Garini

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201 Scopus citations

Abstract

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 LAP2α, 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.

Original language	English
Article number	8044
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9044
State	Published - 24 Aug 2015

Bibliographical note

Funding Information:
We gratefully acknowledge fruitful discussions with Yitzhak Rabin and Eli Barkai (Bar Ilan University), Thomas Dechat and Kevin Gesson (Max F. Perutz Laboratories, Vienna), and Ian T. Young (Delft University). This work was supported in part by the Israel Centers of Research Excellence (ICORE) No. 1902/12 and Israel Science Foundation No. 51/12 (Y.G.); by the European Research Council (Y.S.T); by the Austrian Science Fund (FWF) grant P26492-B20 (R.F.); by the NIGMS Grant RO1 GM094513-01, DOD BCRP Idea Award BC110089 and Presidential Research Award, St Louis University (S.G.) and by the Canadian Institutes of Health Research—CIHR (S.M.).

Funding

We gratefully acknowledge fruitful discussions with Yitzhak Rabin and Eli Barkai (Bar Ilan University), Thomas Dechat and Kevin Gesson (Max F. Perutz Laboratories, Vienna), and Ian T. Young (Delft University). This work was supported in part by the Israel Centers of Research Excellence (ICORE) No. 1902/12 and Israel Science Foundation No. 51/12 (Y.G.); by the European Research Council (Y.S.T); by the Austrian Science Fund (FWF) grant P26492-B20 (R.F.); by the NIGMS Grant RO1 GM094513-01, DOD BCRP Idea Award BC110089 and Presidential Research Award, St Louis University (S.G.) and by the Canadian Institutes of Health Research—CIHR (S.M.).

Funders	Funder number
U.S. Department of Defense	BC110089
National Institute of General Medical Sciences	R01GM094513
Saint Louis University
Canadian Institutes of Health Research
European Commission
Austrian Science Fund	P26492-B20
Israel Science Foundation	51/12
Israeli Centers for Research Excellence	1902/12

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title = "Loss of lamin A function increases chromatin dynamics in the nuclear interior",

abstract = "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 LAP2α, 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.",

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

Abstract

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