PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1
DNA methylation is an epigenetic modification that plays a vital role in a variety of biological processes, including the regulation of gene expression, cell differentiation, early embryonic development, genomic imprinting, and X chromosome inactivation. PGC7 is a maternal factor that maintains DNA...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Xing Wei Yingxiang Liu Weijie Hao Peiwen Feng Lei Zhang Hongni Xue Qunli Zhou Zekun Guo |
| author_facet | Xing Wei Yingxiang Liu Weijie Hao Peiwen Feng Lei Zhang Hongni Xue Qunli Zhou Zekun Guo |
| author_sort | Xing Wei |
| collection | DOAJ |
| description | DNA methylation is an epigenetic modification that plays a vital role in a variety of biological processes, including the regulation of gene expression, cell differentiation, early embryonic development, genomic imprinting, and X chromosome inactivation. PGC7 is a maternal factor that maintains DNA methylation during early embryonic development. One mechanism of action has been identified by analyzing the interactions between PGC7 and UHRF1, H3K9 me2, or TET2/TET3, which reveals how PGC7 regulates DNA methylation in oocytes or fertilized embryos. However, the mechanism by which PGC7 regulates the post-translational modification of methylation-related enzymes remains to be elucidated. This study focused on F9 cells (embryonic cancer cells), which display high levels of PGC7 expression. We found that both knockdown of <i>Pgc7</i> and inhibition of ERK activity resulted in increased genome-wide DNA methylation levels. Mechanistic experiments confirmed that inhibition of ERK activity led to the accumulation of DNMT1 in the nucleus, ERK phosphorylated DNMT1 at ser717, and DNMT1 Ser717-Ala mutation promoted the nuclear localization of DNMT1. Moreover, knockdown of <i>Pgc7</i> also caused downregulation of ERK phosphorylation and promoted the accumulation of DNMT1 in the nucleus. In conclusion, we reveal a new mechanism by which PGC7 regulates genome-wide DNA methylation via phosphorylation of DNMT1 at ser717 by ERK. These findings may provide new insights into treatments for DNA methylation-related diseases. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:45:12Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa1e436450fb4ccb89ea0ed6c892d5bd2023-11-16T20:55:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244309310.3390/ijms24043093PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1Xing Wei0Yingxiang Liu1Weijie Hao2Peiwen Feng3Lei Zhang4Hongni Xue5Qunli Zhou6Zekun Guo7College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, ChinaDNA methylation is an epigenetic modification that plays a vital role in a variety of biological processes, including the regulation of gene expression, cell differentiation, early embryonic development, genomic imprinting, and X chromosome inactivation. PGC7 is a maternal factor that maintains DNA methylation during early embryonic development. One mechanism of action has been identified by analyzing the interactions between PGC7 and UHRF1, H3K9 me2, or TET2/TET3, which reveals how PGC7 regulates DNA methylation in oocytes or fertilized embryos. However, the mechanism by which PGC7 regulates the post-translational modification of methylation-related enzymes remains to be elucidated. This study focused on F9 cells (embryonic cancer cells), which display high levels of PGC7 expression. We found that both knockdown of <i>Pgc7</i> and inhibition of ERK activity resulted in increased genome-wide DNA methylation levels. Mechanistic experiments confirmed that inhibition of ERK activity led to the accumulation of DNMT1 in the nucleus, ERK phosphorylated DNMT1 at ser717, and DNMT1 Ser717-Ala mutation promoted the nuclear localization of DNMT1. Moreover, knockdown of <i>Pgc7</i> also caused downregulation of ERK phosphorylation and promoted the accumulation of DNMT1 in the nucleus. In conclusion, we reveal a new mechanism by which PGC7 regulates genome-wide DNA methylation via phosphorylation of DNMT1 at ser717 by ERK. These findings may provide new insights into treatments for DNA methylation-related diseases.https://www.mdpi.com/1422-0067/24/4/3093PGC7DNA methylationERKphosphorylationDNMT1 |
| spellingShingle | Xing Wei Yingxiang Liu Weijie Hao Peiwen Feng Lei Zhang Hongni Xue Qunli Zhou Zekun Guo PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 International Journal of Molecular Sciences PGC7 DNA methylation ERK phosphorylation DNMT1 |
| title | PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 |
| title_full | PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 |
| title_fullStr | PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 |
| title_full_unstemmed | PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 |
| title_short | PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1 |
| title_sort | pgc7 regulates genome wide dna methylation by regulating erk mediated subcellular localization of dnmt1 |
| topic | PGC7 DNA methylation ERK phosphorylation DNMT1 |
| url | https://www.mdpi.com/1422-0067/24/4/3093 |
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