Fig. 5: Acute and sustained changes in site-specific CpG methylation in CD34+ HSPCs following AZA treatment.
From: Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs
a–d Acute methylation changes at 440140 CpG sites detected in all samples at C1D1 and C1D8 following the first cycle of AZA treatment. a Genomic distribution of CpG sites differentially methylated at C1D8 compared to baseline C1D1 in responders and non-responders. b Upset plot showing overlap of differentially methylated CpG sites between comparison groups. c Network diagram showing enriched pathways for genes mapping to CpGs which are uniquely hypomethylated in responders at C1D8 compared to C1D1 (n = 15488 CpGs). Network diagrams were created with clusterProfiler91 using GO pathways98.CpGs were annotated to genes using HiChIP data from healthy human HSPC subsets55. d Enrichment of CpGs differentially methylated in responders at genomic regions with specific histone marks (H3K27Ac, H3K3me3, H3K27me3) or bound by key transcription factors and genome organisers (FLI1, ERG, PU.1, GATA2, RUNX1, TAL1, LYL1, LMO2, Pol2, CTCF, STAG2) in healthy human HSPC subsets. Plot shows CpG regions hypermethylated (upper) or hypomethylated (lower) at C1D8 compared to C1D1 in responders. e, f Changes in gene expression during cycle 1. e clusterProfiler91 pathway98 enrichment across all patients, irrespective of clinical response, at C1D8 vs C1D1. f Normalised enrichment scores from FSGEA99 analysis for pathways related to blood production in responders compared to non-responders at C1D8.
