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

Sergey V. Ulianov (), Semen A. Doronin, Ekaterina E. Khrameeva, Pavel I. Kos, Artem V. Luzhin, Sergei S. Starikov, Aleksandra A. Galitsyna, Valentina V. Nenasheva, Artem A. Ilyin, Ilya M. Flyamer, Elena A. Mikhaleva, Mariya D. Logacheva, Mikhail S. Gelfand, Alexander V. Chertovich, Alexey A. Gavrilov, Sergey V. Razin and Yuri Y. Shevelyov ()
Additional contact information
Sergey V. Ulianov: Russian Academy of Sciences
Semen A. Doronin: Russian Academy of Sciences
Ekaterina E. Khrameeva: Skolkovo Institute of Science and Technology
Pavel I. Kos: M.V. Lomonosov Moscow State University
Artem V. Luzhin: Russian Academy of Sciences
Sergei S. Starikov: M.V. Lomonosov Moscow State University
Aleksandra A. Galitsyna: Russian Academy of Sciences
Valentina V. Nenasheva: Russian Academy of Sciences
Artem A. Ilyin: Russian Academy of Sciences
Ilya M. Flyamer: University of Edinburgh
Elena A. Mikhaleva: Russian Academy of Sciences
Mariya D. Logacheva: Skolkovo Institute of Science and Technology
Mikhail S. Gelfand: Skolkovo Institute of Science and Technology
Alexander V. Chertovich: M.V. Lomonosov Moscow State University
Alexey A. Gavrilov: Russian Academy of Sciences
Sergey V. Razin: Russian Academy of Sciences
Yuri Y. Shevelyov: Russian Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09185-y

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