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. 2019 Jan 15;8:e40197. doi: 10.7554/eLife.40197

Figure 2. Early gene body mCH accumulation predicts later transcriptional downregulation.

(A and B) Normalized gene body mCH (A) and transcript abundance (B) for genes ranked by early mCH accumulation at BAM 5d. Early mCH accumulation is strongly correlated to gene repression in BAM 22d iN cells, and both upregulated and downregulated genes in BAM 13d iN cells. (C) Significance (hypergeometric test) of the enrichment in down- and up- regulated genes for BAM 13d and BAM 22d iN cells. (D and E) Gene body mCH dynamics of static, down- and up- regulated genes with different transcripts abundances - log2(RPKM +1) between 0 and 1 (D), between 4 and 5 (E) during iN cell reprogramming. (F) Gene body mCH level of cerebellum developmentally (P60 vs. P7) regulated genes that were actively expressed (RPKM >3). (G) Alteration of cerebellum gene expression by Nes-Cre;Dnmt3a-/- for developmentally regulated genes.

Figure 2.

Figure 2—figure supplement 1. Dynamically regulated genes are enriched in CH methylation during direct reprogramming and cerebellum development. .

Figure 2—figure supplement 1.

(A and B) Gene body mCH dynamics of developmentally static, down- and up- regulated genes with different transcripts abundances - log2(RPKM +1) between 2 and 3. (A), between 6 and 7 (B). (C) Genes under the regulation of polycomb repressive complex (H3K27me3+) show similar misregulation in Dnmt3a cKO as genes not regulated by polycomb complex (H3K27me3-). (D) Developmentally upregulated genes in cerebellum accumulate more hydroxymethylcytosine in the CG dinucleotide context than developmentally downregulated genes and static genes.