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, Yuri Y. Shevelyov

    Research output: Contribution to journalArticlepeer-review

    50 Citations (Scopus)

    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.

    Original languageEnglish
    Article number1176
    JournalNature Communications
    Volume10
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2019

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