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 en...

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Bibliographic Details
Published in:Gene and genome editing 2023-06, Vol.5, p.100023, Article 100023
Main Authors: Bischoff, Nadja, Wimberger, Sandra, Kühn, Ralf, Laugesen, Anne, Turan, Volkan, Larsen, Brian Daniel, Sørensen, Claus Storgaard, Helin, Kristian, Bennett, Eric Paul, Maresca, Marcello, Brakebusch, Cord
Format: Article
Language:English
Subjects:
Chromatin modification
CRISPR-Cas9
HDR
Histone methylation
NHEJ
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Summary: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.
ISSN:2666-3880
2666-3880
DOI:10.1016/j.ggedit.2022.100023