Fig. 5. Down syndrome (DS)-associated differentially methylated region (DMR) overlapping FLI1 promoter region.
a DS-associated DMR (Šidák-corrected P = 1.65 × 10−78 from comb-p), which included 19 CpGs, had a mean Δβ-value = +0.132 between DS (teal, N = 196) and non-DS (red, N = 439) newborns, and overlapped a promoter of FLI1 transcript variant 4. The position of the DMR (brown horizontal bar) is shown relative to the FLI1 gene in the UCSC Genome Browser (https://genome.ucsc.edu/), along with tracks for chromatin accessibility (DNase I clusters, darkness corresponds to signal strength) and histone modifications (H3K4me3, H3K27ac), CpG islands (green), and a custom track displaying positions of the array CpG probes (blue). b Violin plot showing normalized FLI1 expression derived from single-cell qRT-PCR on index-sorted FL myeloid progenitors with megakaryocyte–erythroid potential (Lin−CD34+CD38+CD45RA−) from non-DS (N = 3) and DS (N = 3) subjects. FLI1 expression was significantly reduced in DS myeloid progenitor cells (N = 292) compared with non-DS cells (N = 412) (P = 2.20 × 10−16, two-sided Wilcoxon rank-sum test). Horizontal lines represent the median.