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Nat Commun. 2019 Mar 12;10(1):1176. doi: 10.1038/s41467-019-09185-y.

Nuclear lamina integrity is required for proper spatial organization of chromatin in Drosophila.

Author information

1
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia. sergey.v.ulyanov@gmail.com.
2
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia. sergey.v.ulyanov@gmail.com.
3
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
4
Skolkovo Institute of Science and Technology, Skolkovo, 143026, Russia.
5
Institute for Information Transmission Problems (the Kharkevich Institute), Russian Academy of Sciences, Moscow, 127051, Russia.
6
Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.
7
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
8
Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.
9
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
10
Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, 119234, Russia.
11
Russia Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420012, Russia.
12
Faculty of Computer Science, National Research University Higher School of Economics, Moscow, 125319, Russia.
13
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.
14
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. shevelev@img.ras.ru.

Abstract

How the nuclear lamina (NL) impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to chromatin compaction and repositioning from the nuclear envelope. This increases the chromatin density in a fraction of topologically-associating domains (TADs) enriched in active chromatin and enhances interactions between active and inactive chromatin. Importantly, upon NL disruption the NL-associated TADs become more acetylated at histone H3 and less compact, while background transcription is derepressed. Two-colour FISH confirms that a TAD becomes less compact following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.

PMID:
30862957
PMCID:
PMC6414625
DOI:
10.1038/s41467-019-09185-y
[Indexed for MEDLINE]
Free PMC Article

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