Proteomics

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Lamin A acetylation shapes nuclear architecture and safeguards genomic integrity

ABSTRACT: The nuclear lamina constitutes more than a structural scaffold for the nucleus and plays a crucial role in protection of genomic integrity. Here we report that the loss of the lysine acetyl-transferase (KAT) MOF leads to nuclear architecture defects during interphase including micronuclei formation. We identify Lamin A/C, a major component of the nuclear lamina, to be an acetylation target of MOF. A point mutation in Lamin A phenocopies nuclear morphology defects observed upon Mof-deletion. Through single cell DNA sequencing, we reveal that either loss of Mof or Lamin A mutation result in extensive genomic instability, including chromothripsis. Our work establishes MOF-dependent Lamin acetylation as a key regulator of nuclear architecture maintenance in mammals.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Fibroblast, Embryonic Stem Cell

SUBMITTER: Witold Szymanski  

LAB HEAD: Gerhard Mittler

PROVIDER: PXD008539 | Pride | 2019-08-16

REPOSITORIES: Pride

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Publications

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. HDA  ...[more]

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