Fig. 4: Down syndrome (DS)-associated differentially methylated region (DMR) overlapping RUNX1 regulatory region.
From: The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
a DS-associated DMR (Šidák-corrected P value = 2.30 × 10−84 from comb-p), which included 11 CpGs, had the greatest mean Δβ-value (+0.273) between DS (teal, N = 196) and non-DS (red, N = 439) newborns, and overlapped a large regulatory region that encompasses the RUNX1 proximal P2 promoter and the first exon of the P2 isoform, or exon 4 of the P1 isoform. The position of the DMR (brown horizontal bar) is shown relative to the RUNX1 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). High coverage of CpG probes is shown both at the proximal P2 and distal P1 promoters of RUNX1. b Violin plot showing normalized RUNX1 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. RUNX1 expression was significantly increased in DS myeloid progenitor cells (N = 292) compared with non-DS cells (N = 412) (P = 3.81 × 10−5, two-sided Wilcoxon rank-sum test). Horizontal lines represent the median.
