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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Karoutas A,Szymanski W,Rausch T,Guhathakurta S,Rog-Zielinska EA,Peyronnet R,Seyfferth J,Chen HR,de Leeuw R,Herquel B,Kimura H,Mittler G,Kohl P,Medalia O,Korbel JO,Akhtar Adoi
10.1038/s41556-019-0397-zsubject
Has Abstractpub_date
2019-10-01 00:00:00pages
1248-1260issue
10eissn
1465-7392issn
1476-4679pii
10.1038/s41556-019-0397-zjournal_volume
21pub_type
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