Extended Data Fig. 4: Relationship between CpG methylation and chromatin accessibility at the STR enhancer cluster.

For each Fiber-seq sequencing read at this site, shown is the per-molecule m6A-marked chromatin accessibility stencils (left), as well as the per-molecule methylation status of CpG dinucleotides (right) for the same reads. CpG methylation status is indicated using a color gradient from blue to red, with blue indicating unmethylated CpGs, and red indicating methylated CpGs, and the shading according to the precision of the methylation calls according to Primrose. Reads are separated out by sample, as well as by haplotype within the RTSH samples. Reads are then ranked based on the CpG methylation status surrounding the STR site, with hypo-CpG methylated reads being on top. This reveals that individual chromatin fibers harboring chromatin accessibility at this enhancer cluster similarly had hypo-CpG methylation of the surrounding CpG dinucleotides. However, hypo-CpG methylation of the surrounding CpGs was similarly observed on fibers lacking chromatin accessibility at elements 1–3, indicating that hypo-CpG methylation is necessary, but not sufficient for actuating this codependent enhancer cluster.