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The methylation inhibitor 3DZNep promotes HDR pathway choice during CRISPR-Cas9 genome editing

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Item Type:Article
Title:The methylation inhibitor 3DZNep promotes HDR pathway choice during CRISPR-Cas9 genome editing
Creators Name:Bischoff, N. and Wimberger, S. and Kuehn, R. and Laugesen, A. and Turan, V. and Larsen, B.D. and Sørensen, C.S. and Helin, K. and Bennett, E.P. and Maresca, M. and Brakebusch, C.
Abstract: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.
Keywords:CRISPR-Cas9, Histone Methylation, Chromatin Modification, HDR, NHEJ
Source:Gene and Genome Editing
ISSN:2666-3880
Publisher:Elsevier
Volume:5
Page Range:100023
Date:June 2023
Official Publication:http://doi.org/10.1016/j.ggedit.2022.100023

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