Fig. 3
VCD patients exhibit hypomethylation of CpG in CCL11 promoter region, which are hypermethylated upon B12 supplementation. A = a lollipop plot depicting the methylation level fold change of DML in the promoter region and proximal portion of the first exon of CCL11. B, C, and D = The fold change methylation levels of CpG positions were compared between groups using an unpaired t-test. Values next to lollipops represent correlation coefficients (Pearson or Spearman) with statistical significance (* P < 0.05 or ** P < 0.01) between methylation level fold change in each DML and gene expression values. In the schematic representation of the analyzed gene region, the black line represents the CCL11 promoter region, and the black blocks delimit the 5’ UTR region (thin block) and proximal portion of the first exon of the gene (thick block). The red bold dash indicates the transcription start site of CCL11, and the orange boxes indicate predicted transcription factor binding sites. Purple lines correspond to the DML at coordinates (GRCh38/hg38): a = chr17: 34,283,605; b = chr17: 34,283,701; c = chr17: 34,285,656. In the graphs, black-outlined circles or squares denote individuals who attended the 12-month follow-up appointment. In all other cases, both circles and squares represent individuals who attended the 6-month follow-up appointment. Line at mean ± standard deviation. *P < 0.05. DML = differentially methylated locus; TSS = transcription start site. Suffixes: A = endpoint A (whole peripheral blood cultures (WPBC) incubated with excipient); B = endpoint B (WPBC incubated with 1 nM B12).
