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. 2021 Jan 27;12:606. doi: 10.1038/s41467-020-20672-5

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a TIDE analysis of variants of Cas9 and TALEN that target different heterochromatin and euchromatin loci. 50% of the heterochromatin loci are modified more efficiently by TALENs than Cas9 (top). Cas9 has a higher editing efficiency than TALE in the euchromatin regions (bottom). TALENs with the highest predicted cutting efficiency were designed using CHOPCHOP and SAPTA. gRNAs with the highest predicted cutting efficiency were designed using Benchling and CHOPCHOP. TALEN samples are compared to Cas9-gRNA samples by a 2-tailed t test for n > 2. n = {2,3,4,5,6} biological replicates. Data are presented as mean values ± SEM. p < 0.05*, p < 0.01**, p < 0.001***. p-values are given in brackets: Chr3_2 (0.2755, 0.05), Chr4 (0.0096, 0.0171), Chr7 (0.0014, 6.02e-5), Chr10_1 (0.00069, 0.00033), Chr17_1 (0.00179,0.00169), Chr17_2 (0.0027,0.0326), EMX1 (0.0999), TPCN2 (0.0077), NRG2 (0.0025), DNMT1 (0.0274). Source data are provided as a Source Data file. b Illustration of Cas9 and TALE target-search model in heterochromatin. Cas9 becomes trapped in compact heterochromatic structures, whereas TALE can efficiently navigate the heterochromatin.