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. 2020 Mar 11;9:e52981. doi: 10.7554/eLife.52981

Figure 3. RNA-seq from sorted striatal inhibitory neurons of WT and cKO mice reveal MeCP2 is a restricted reader for Dnmt3a dependent methylation.

(A) RNA-seq data of sorted WT vs Dnmt3a cKO or Mecp2 cKO striatal inhibitory neurons that also express the INTACT allele. Red dots represent genes with altered expression in the knockout cells (padj <0.01). (B) Differentially expressed genes (DEGs) that overlap between knockout models. Inhibitory neurons that lack MeCP2 share ~40% of the same DEGs as the same neurons that lack Dnmt3a. Only ~12% of DEGs in inhibitory neurons that lack Dnmt3a are shared with the same neurons that lack MeCP2. (C) Plot of log2 fold-change for DEGs in Dnmt3a cKO and Mecp2 cKO models. DEGs that are only significantly misregulated in the Dnmt3a cKO model, only significantly misregulated in the Mecp2 cKO model, or common to both models are colored in blue, green, or orange, respectively. The plot shows that the DEGs common to both models have similar degree and direction of change.

Figure 3.

Figure 3—figure supplement 1. The percentage of DEGs that overlap between cKO mouse models broken down as a function of (A) p-value, (B) direction of change (down- or up-regulated), (C) gene length.

Figure 3—figure supplement 1.

Figure 3—figure supplement 2. The percentage of DEGs that overlap between parvalbumin (PV) and vasoactive intestinal polypeptide (VIP) neurons in the mouse cortex from Dnmt3a cKO (Nestin-Cre) and Mecp2 KO mouse models.

Figure 3—figure supplement 2.

The data are a re-analysis of single-nuclear RNA sequencing (Stroud et al., 2017). The percentages are shown as all genes and genes broken down by direction of change (down- or up-regulated) for (A) PV and (B) VIP neurons. Consistent with our data there are few DEGs significantly misregulated in Dnmt3a cKO mice that are also significantly misregulated in the same neurons that lack MeCP2. Notably, our data show a significantly higher overlap of genes (40%) misregualted in Mecp2 cKO that are also misregulated in the Dnmt3a cKO.