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  The NSL complex maintains nuclear architecture stability via lamin A/C acetylation

Karoutas, A., Szymanski, W., Rausch, T., Guhathakurta, S., Rog-Zielinska, E. A., Peyronnet, R., et al. (2019). The NSL complex maintains nuclear architecture stability via lamin A/C acetylation. Nature Cell Biology, 21, 1248-1260. doi:org/10.1038/s41556-019-0397-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-1C34-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-1C35-1
Genre: Journal Article

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 Creators:
Karoutas, Adam1, Author              
Szymanski, Witold1, Author              
Rausch, Tobias2, Author
Guhathakurta, Sukanya1, Author              
Rog-Zielinska, Eva A.2, Author
Peyronnet, Remi2, Author
Seyfferth, Janine1, Author
Chen, Hui-Ru1, Author
de Leeuw, Rebecca2, Author
Herquel, Benjamin2, Author
Kimura, Hiroshi2, Author
Mittler, Gerhard1, Author              
Kohl, Peter2, Author
Medalia, Ohad1, Author
Korbel, Jan O. 2, Author
Akhtar, Asifa1, Author              
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              
2External Organizations, ou_persistent22              

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 Abstract: While nuclear lamina abnormalities are hallmarks of human diseases, their interplay with epigenetic regulators and precise epigenetic landscape remain poorly understood. Here, we show that loss of the lysine acetyltransferase MOF or its associated NSL-complex members KANSL2 or KANSL3 leads to a stochastic accumulation of nuclear abnormalities with genomic instability patterns including chromothripsis. SILAC-based MOF and KANSL2 acetylomes identified lamin A/C as an acetylation target of MOF. HDAC inhibition or acetylation-mimicking lamin A derivatives rescue nuclear abnormalities observed in MOF-deficient cells. Mechanistically, loss of lamin A/C acetylation resulted in its increased solubility, defective phosphorylation dynamics and impaired nuclear mechanostability. We found that nuclear abnormalities include EZH2-dependent histone H3 Lys 27 trimethylation and loss of nascent transcription. We term this altered epigenetic landscape “heterochromatin enrichment in nuclear abnormalities” (HENA). Collectively, the NSL-complex-dependent lamin A/C acetylation provides a mechanism that maintains nuclear architecture and genome integrity.

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Language(s): eng - English
 Dates: 2019-10
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: org/10.1038/s41556-019-0397-z
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Title: Nature Cell Biology
  Other : 'Nat. Cell Biol.'
Source Genre: Journal
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Publ. Info: London : Macmillan Magazines Ltd.
Pages: - Volume / Issue: 21 Sequence Number: - Start / End Page: 1248 - 1260 Identifier: ISSN: 1465-7392
CoNE: https://pure.mpg.de/cone/journals/resource/954925625310