Histone malonylation is regulated by SIRT5 and KAT2A

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Histone malonylation is regulated by SIRT5 and KAT2A. / Zhang, Ran; Bons, Joanna; Scheidemantle, Grace; Liu, Xiaojing; Bielska, Olga; Carrico, Chris; Rose, Jacob; Heckenbach, Indra; Scheibye-Knudsen, Morten; Schilling, Birgit; Verdin, Eric.

In: iScience, Vol. 26, No. 3, 106193, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zhang, R, Bons, J, Scheidemantle, G, Liu, X, Bielska, O, Carrico, C, Rose, J, Heckenbach, I, Scheibye-Knudsen, M, Schilling, B & Verdin, E 2023, 'Histone malonylation is regulated by SIRT5 and KAT2A', iScience, vol. 26, no. 3, 106193. https://doi.org/10.1016/j.isci.2023.106193

APA

Zhang, R., Bons, J., Scheidemantle, G., Liu, X., Bielska, O., Carrico, C., Rose, J., Heckenbach, I., Scheibye-Knudsen, M., Schilling, B., & Verdin, E. (2023). Histone malonylation is regulated by SIRT5 and KAT2A. iScience, 26(3), [106193]. https://doi.org/10.1016/j.isci.2023.106193

Vancouver

Zhang R, Bons J, Scheidemantle G, Liu X, Bielska O, Carrico C et al. Histone malonylation is regulated by SIRT5 and KAT2A. iScience. 2023;26(3). 106193. https://doi.org/10.1016/j.isci.2023.106193

Author

Zhang, Ran ; Bons, Joanna ; Scheidemantle, Grace ; Liu, Xiaojing ; Bielska, Olga ; Carrico, Chris ; Rose, Jacob ; Heckenbach, Indra ; Scheibye-Knudsen, Morten ; Schilling, Birgit ; Verdin, Eric. / Histone malonylation is regulated by SIRT5 and KAT2A. In: iScience. 2023 ; Vol. 26, No. 3.

Bibtex

@article{f843bca0063b457f9e99d3f5a05f19a0,

title = "Histone malonylation is regulated by SIRT5 and KAT2A",

abstract = "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 malonyl donor, 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 in particular reduced histone malonylation levels. By mass spectrometry, H2B_K5 was highly malonylated and 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.",

keywords = "Biological sciences, Molecular biology, Omics, Proteomics",

author = "Ran Zhang and Joanna Bons and Grace Scheidemantle and Xiaojing Liu and Olga Bielska and Chris Carrico and Jacob Rose and Indra Heckenbach and Morten Scheibye-Knudsen and Birgit Schilling and Eric Verdin",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

doi = "10.1016/j.isci.2023.106193",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "3",

}

RIS

TY - JOUR

T1 - Histone malonylation is regulated by SIRT5 and KAT2A

AU - Zhang, Ran

AU - Bons, Joanna

AU - Scheidemantle, Grace

AU - Liu, Xiaojing

AU - Bielska, Olga

AU - Carrico, Chris

AU - Rose, Jacob

AU - Heckenbach, Indra

AU - Scheibye-Knudsen, Morten

AU - Schilling, Birgit

AU - Verdin, Eric

PY - 2023

Y1 - 2023

N2 - 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 malonyl donor, 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 in particular reduced histone malonylation levels. By mass spectrometry, H2B_K5 was highly malonylated and 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.

AB - 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 malonyl donor, 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 in particular reduced histone malonylation levels. By mass spectrometry, H2B_K5 was highly malonylated and 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.

KW - Biological sciences

KW - Molecular biology

KW - Omics

KW - Proteomics

U2 - 10.1016/j.isci.2023.106193

DO - 10.1016/j.isci.2023.106193

M3 - Journal article

C2 - 36879797

AN - SCOPUS:85148670063

VL - 26

JO - iScience

JF - iScience

SN - 2589-0042

IS - 3

M1 - 106193

ER -

ID: 340109492