Nadja Bischoff , Sandra Wimberger , Ralf Kühn , Anne Laugesen , Volkan Turan , Brian Daniel Larsen , Claus Storgaard Sørensen , Kristian Helin , Eric Paul Bennett , Marcello Maresca , Cord Brakebusch
{"title":"甲基化抑制剂3DZNep在CRISPR-Cas9基因组编辑过程中促进HDR途径的选择","authors":"Nadja Bischoff , Sandra Wimberger , Ralf Kühn , Anne Laugesen , Volkan Turan , Brian Daniel Larsen , Claus Storgaard Sørensen , Kristian Helin , Eric Paul Bennett , Marcello Maresca , Cord Brakebusch","doi":"10.1016/j.ggedit.2022.100023","DOIUrl":null,"url":null,"abstract":"<div><p>Alteration of specific epigenetic marks might promote homology directed repair (HDR) during CRISPR-Cas9 genome editing. Testing several epigenetic inhibitors in a traffic light reporter assay, the histone methylation inhibitor 3DZNep showed a significant HDR promoting effect, while non-homologous end joining mediated repair was not significantly changed. This HDR promoting effect was largely independent of the target gene and its expression levels but showed a limited cell type specificity. HDR promotion was independent of the best described target of 3DZNep, the H3K27 methyltransferase EZH2, and of altered gene expression, but correlated partially with increased frequency of S/G2 cell cycle stage.</p></div>","PeriodicalId":73137,"journal":{"name":"Gene and genome editing","volume":"5 ","pages":"Article 100023"},"PeriodicalIF":0.0000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The methylation inhibitor 3DZNep promotes HDR pathway choice during CRISPR-Cas9 genome editing\",\"authors\":\"Nadja Bischoff , Sandra Wimberger , Ralf Kühn , Anne Laugesen , Volkan Turan , Brian Daniel Larsen , Claus Storgaard Sørensen , Kristian Helin , Eric Paul Bennett , Marcello Maresca , Cord Brakebusch\",\"doi\":\"10.1016/j.ggedit.2022.100023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Alteration of specific epigenetic marks might promote homology directed repair (HDR) during CRISPR-Cas9 genome editing. Testing several epigenetic inhibitors in a traffic light reporter assay, the histone methylation inhibitor 3DZNep showed a significant HDR promoting effect, while non-homologous end joining mediated repair was not significantly changed. This HDR promoting effect was largely independent of the target gene and its expression levels but showed a limited cell type specificity. HDR promotion was independent of the best described target of 3DZNep, the H3K27 methyltransferase EZH2, and of altered gene expression, but correlated partially with increased frequency of S/G2 cell cycle stage.</p></div>\",\"PeriodicalId\":73137,\"journal\":{\"name\":\"Gene and genome editing\",\"volume\":\"5 \",\"pages\":\"Article 100023\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gene and genome editing\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666388022000132\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene and genome editing","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666388022000132","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The methylation inhibitor 3DZNep promotes HDR pathway choice during CRISPR-Cas9 genome editing
Alteration of specific epigenetic marks might promote homology directed repair (HDR) during CRISPR-Cas9 genome editing. Testing several epigenetic inhibitors in a traffic light reporter assay, the histone methylation inhibitor 3DZNep showed a significant HDR promoting effect, while non-homologous end joining mediated repair was not significantly changed. This HDR promoting effect was largely independent of the target gene and its expression levels but showed a limited cell type specificity. HDR promotion was independent of the best described target of 3DZNep, the H3K27 methyltransferase EZH2, and of altered gene expression, but correlated partially with increased frequency of S/G2 cell cycle stage.
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