Fig. 2

Overview of the relationship between genetic changes, promoter 5mC/5hmC levels and gene expression. a Summary of the molecular details of the genes involved in the turnover of cytosine modifications. Differential transcript levels between tumour and margin (log₂FC where FC = (TPM_tumour + 0.01)/(TPM_margin + 0.01)) and mean transcript levels ((log₂(TPM_tumour + 0.01) + (log₂(TPM_margin + 0.01))/2), SNVs (1: presence and 0: absence), CNVs (↑: gain of copies, 0: diploid and ↓: loss of copies and LOH: loss of heterozygosity), promoter CpG counts, and promoter 5mC and 5hmC levels (%) in margin (M) and tumour (T), which are colour-coded as shown in the legend. Genes bearing genomic alterations in glioma progression²⁴ were also examined (Supplementary Fig. 1). b Average and base resolution maps of 5mC and 5hmC levels and changes in transcript abundance between margin and tumour in the promoter region (1 kb upstream of the transcription start site) of the TET2 (chr4:106066031-106067031, 22 CpG sites) and TET3 (chr2:74272449-74273449, 6 CpG sites) genes. c Cytosine modifications and changes in transcript levels across all gene promoters containing CpG sites (n = 18,653) in margin. Promoters are divided into four sectors according to the levels of 5mC and 5hmC: sectors {1, 2} and {3, 4} contain low and high levels of 5mC according to the first and third terciles (3.2 and 23.2%) of the %5mC distribution respectively (horizontal axis). The median level of 5hmC (7.4%) is used to separate low and high 5hmC levels (vertical axis). The inset box plot displays the transcript levels for each sector. d Promoters are divided into three types depending on whether 5mC, 5hmC or C is more abundant within the promoter. The inset box plot illustrates the transcript levels for each promoter type. e Relationship between differential transcript levels (log₂FC) and differences in 5hmC levels between tumour and margin in gene promoters containing more than 10 CpG sites (n = 15,716). The top ten promoters with larger changes in 5hmC levels are labelled