The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase
Abstract Background Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Epigenetics & Chromatin |
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| Online Access: | https://doi.org/10.1186/s13072-023-00494-7 |
| _version_ | 1797451476034912256 |
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| author | Eva Monte-Serrano Patricia Morejón-García Ignacio Campillo-Marcos Aurora Campos-Díaz Elena Navarro-Carrasco Pedro A. Lazo |
| author_facet | Eva Monte-Serrano Patricia Morejón-García Ignacio Campillo-Marcos Aurora Campos-Díaz Elena Navarro-Carrasco Pedro A. Lazo |
| author_sort | Eva Monte-Serrano |
| collection | DOAJ |
| description | Abstract Background Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be coordinated, a role that may be mediated by chromatin kinases such as VRK1, which phosphorylates histones H3 and H2A. Methods The effect of VRK1 depletion and VRK1 inhibitor, VRK-IN-1, on the acetylation and methylation of histone H3 in K4, K9 and K27 was determined under different conditions, arrested or proliferating cells, in A549 lung adenocarcinoma and U2OS osteosarcoma cells. Results Chromatin organization is determined by the phosphorylation pattern of histones mediated by different types of enzymes. We have studied how the VRK1 chromatin kinase can alter the epigenetic posttranslational modifications of histones by using siRNA, a specific inhibitor of this kinase (VRK-IN-1), and of histone acetyl and methyl transferases, as well as histone deacetylase and demethylase. Loss of VRK1 implicated a switch in the state of H3K9 posttranslational modifications. VRK1 depletion/inhibition causes a loss of H3K9 acetylation and facilitates its methylation. This effect is similar to that of the KAT inhibitor C646, and to KDM inhibitors as iadademstat (ORY-1001) or JMJD2 inhibitor. Alternatively, HDAC inhibitors (selisistat, panobinostat, vorinostat) and KMT inhibitors (tazemetostat, chaetocin) have the opposite effect of VRK1 depletion or inhibition, and cause increase of H3K9ac and a decrease of H3K9me3. VRK1 stably interacts with members of these four enzyme families. However, VRK1 can only play a role on these epigenetic modifications by indirect mechanisms in which these epigenetic enzymes are likely targets to be regulated and coordinated by VRK1. Conclusions The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation in lysines 4, 9 and 27. VRK1 is a master regulator of chromatin organization associated with its specific functions, such as transcription or DNA repair. |
| first_indexed | 2024-03-09T14:54:12Z |
| format | Article |
| id | doaj.art-676b1382522c4af5bf97929acd574fdf |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-03-09T14:54:12Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-676b1382522c4af5bf97929acd574fdf2023-11-26T14:16:22ZengBMCEpigenetics & Chromatin1756-89352023-05-0116112010.1186/s13072-023-00494-7The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinaseEva Monte-Serrano0Patricia Morejón-García1Ignacio Campillo-Marcos2Aurora Campos-Díaz3Elena Navarro-Carrasco4Pedro A. Lazo5Molecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de SalamancaAbstract Background Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be coordinated, a role that may be mediated by chromatin kinases such as VRK1, which phosphorylates histones H3 and H2A. Methods The effect of VRK1 depletion and VRK1 inhibitor, VRK-IN-1, on the acetylation and methylation of histone H3 in K4, K9 and K27 was determined under different conditions, arrested or proliferating cells, in A549 lung adenocarcinoma and U2OS osteosarcoma cells. Results Chromatin organization is determined by the phosphorylation pattern of histones mediated by different types of enzymes. We have studied how the VRK1 chromatin kinase can alter the epigenetic posttranslational modifications of histones by using siRNA, a specific inhibitor of this kinase (VRK-IN-1), and of histone acetyl and methyl transferases, as well as histone deacetylase and demethylase. Loss of VRK1 implicated a switch in the state of H3K9 posttranslational modifications. VRK1 depletion/inhibition causes a loss of H3K9 acetylation and facilitates its methylation. This effect is similar to that of the KAT inhibitor C646, and to KDM inhibitors as iadademstat (ORY-1001) or JMJD2 inhibitor. Alternatively, HDAC inhibitors (selisistat, panobinostat, vorinostat) and KMT inhibitors (tazemetostat, chaetocin) have the opposite effect of VRK1 depletion or inhibition, and cause increase of H3K9ac and a decrease of H3K9me3. VRK1 stably interacts with members of these four enzyme families. However, VRK1 can only play a role on these epigenetic modifications by indirect mechanisms in which these epigenetic enzymes are likely targets to be regulated and coordinated by VRK1. Conclusions The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation in lysines 4, 9 and 27. VRK1 is a master regulator of chromatin organization associated with its specific functions, such as transcription or DNA repair.https://doi.org/10.1186/s13072-023-00494-7Histone H3AcetylationMethylationKinaseChromatinVRK-IN-1 |
| spellingShingle | Eva Monte-Serrano Patricia Morejón-García Ignacio Campillo-Marcos Aurora Campos-Díaz Elena Navarro-Carrasco Pedro A. Lazo The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase Epigenetics & Chromatin Histone H3 Acetylation Methylation Kinase Chromatin VRK-IN-1 |
| title | The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase |
| title_full | The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase |
| title_fullStr | The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase |
| title_full_unstemmed | The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase |
| title_short | The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase |
| title_sort | pattern of histone h3 epigenetic posttranslational modifications is regulated by the vrk1 chromatin kinase |
| topic | Histone H3 Acetylation Methylation Kinase Chromatin VRK-IN-1 |
| url | https://doi.org/10.1186/s13072-023-00494-7 |
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