Description
The posttranslational modification lysine malonylation is found in many proteins, including histones. However, it remains unclear whether histone malonylation is regulated or functionally relevant. Here, we report that availability of malonyl-co-enzyme A (malonyl-CoA), an endogenous provider of malonyl groups, affects lysine malonylation, and that the deacylase SIRT5 selectively reduces malonylation of histones. To determine if histone malonylation is enzymatically catalyzed, we knocked down each of the 22 lysine acetyltransferases (KATs) to test their malonyltransferase potential. KAT2A knockdown reduced and KAT2A overexpression increased levels of histone malonylation, respectively. By mass spectrometry, H2B_K5 was highly malonylated and significantly regulated by SIRT5 in mouse brain and liver. Acetyl-CoA carboxylase (ACC), the malonyl-CoA producing enzyme, was partly localized in the nucleolus, and histone malonylation increased nucleolar area and ribosomal RNA expression. Levels of global lysine malonylation and ACC expression were higher in older mouse brains than younger mice. These experiments highlight the role of histone malonylation in ribosomal gene expression.
[doi:10.25345/C5Z60C58X]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Aging ; Histone ; Malonylation ; Nucleolus ; SIRT5
Contact
Principal Investigators:
(in alphabetical order)
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Birgit Schilling, Buck Institute, USA
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JoannaBons
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