Histone malonylation is regulated by SIRT5 and KAT2A
Summary: 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223002705 |
| _version_ | 1797894641495834624 |
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| author | Ran Zhang Joanna Bons Grace Scheidemantle Xiaojing Liu Olga Bielska Chris Carrico Jacob Rose Indra Heckenbach Morten Scheibye-Knudsen Birgit Schilling Eric Verdin |
| author_facet | Ran Zhang Joanna Bons Grace Scheidemantle Xiaojing Liu Olga Bielska Chris Carrico Jacob Rose Indra Heckenbach Morten Scheibye-Knudsen Birgit Schilling Eric Verdin |
| author_sort | Ran Zhang |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-10T07:13:40Z |
| format | Article |
| id | doaj.art-163eef16f75240ae901b4483744024e4 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T07:13:40Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-163eef16f75240ae901b4483744024e42023-02-26T04:27:45ZengElsevieriScience2589-00422023-03-01263106193Histone malonylation is regulated by SIRT5 and KAT2ARan Zhang0Joanna Bons1Grace Scheidemantle2Xiaojing Liu3Olga Bielska4Chris Carrico5Jacob Rose6Indra Heckenbach7Morten Scheibye-Knudsen8Birgit Schilling9Eric Verdin10Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Nørregade 10, Copenhagen, DenmarkCenter for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Nørregade 10, Copenhagen, DenmarkBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223002705Biological sciencesMolecular biologyOmicsProteomics |
| spellingShingle | Ran Zhang Joanna Bons Grace Scheidemantle Xiaojing Liu Olga Bielska Chris Carrico Jacob Rose Indra Heckenbach Morten Scheibye-Knudsen Birgit Schilling Eric Verdin Histone malonylation is regulated by SIRT5 and KAT2A iScience Biological sciences Molecular biology Omics Proteomics |
| title | Histone malonylation is regulated by SIRT5 and KAT2A |
| title_full | Histone malonylation is regulated by SIRT5 and KAT2A |
| title_fullStr | Histone malonylation is regulated by SIRT5 and KAT2A |
| title_full_unstemmed | Histone malonylation is regulated by SIRT5 and KAT2A |
| title_short | Histone malonylation is regulated by SIRT5 and KAT2A |
| title_sort | histone malonylation is regulated by sirt5 and kat2a |
| topic | Biological sciences Molecular biology Omics Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223002705 |
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