Figure 5. Persistent DMRs affect F1 bone marrow expression profiles.
(A) Transcription factor (TF) binding sites enriched in persistent DMRs. ‘Adjusted p-value’: Bonferroni-corrected AME p-value. ‘% persistent DMRs’, ‘% background’: percentage of tiles containing the TF binding site. ‘Change in binding’, relative enrichment of mCpGs in bisulfite-SELEX data from Yin et al. (2017). (B) Genes differentially expressed in healthy Kdm6a F1 (top) or diseased Kdm6a F1 (bottom) vs. control F1 bone marrow. (C) Top, gene model of Runx2 with location of a persistent DMR in the first intron (red circle). Middle, sequence of the DMR including ELK1 binding site and affected CpG (red box). Bottom, RRBS DNA methylation levels at the boxed CpG in sperm and F1 bone marrow. (D) Expression of Runx2 in F1 bone marrow. *p<0.05, Welch’s t-test. (E) Principal component analysis of 134 differentially expressed RUNX2 target genes. Circles, individual samples; open squares, centroid; ellipses, 95% confidence interval. See Figure 5—source data 1.