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. 2020 Oct 1;34(19-20):1373–1391. doi: 10.1101/gad.340695.120

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© 2020 Lasman et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 6. — Ythdf triple-KO has a dramatic effect on gene expression. (A) Hierarchical clustering of samples based on Pearson correlation, showing that single-KO samples are highly similar to WT. (B) Number of differentially expressed genes in each of the KO cell lines, compared with WT. (Black) Down-regulated genes, (gray) up-regulated genes. (C) RNA-seq and m⁶A methylation landscape of selected genes. Normalized coverage is presented. Only Nanog and Dnmt3l are m⁶A methylated. Dnmt3l, Zscan4a, Zscan4b, Zscan4d, and Dppa3 are overexpressed in triple-KO. (D) Enrichment of up-regulated genes in each category, to early embryo genes (Gao et al. 2017). Genes that are up-regulated in KO of Ythdf1 and Ythdf3 are specifically enriched for two-cell embryo genes. (E) Normalized expression of Ythdf1, Ythdf2, and Ythdf3, as measured in early mouse embryo (Gao et al. 2017). (F) CLIP coverage over m⁶A peaks of Ythdf readers as measured in humans (n = 41,885) (Patil et al. 2016), and in mice (n = 9861), showing high correlation between coverage by different Ythdf readers.