(
A) HOMER-identified enriched motifs in EC-only LMRs and ATAC-seq peaks shared between all four EC subtypes. Frequency of the indicated motif as a function of distance from the center of these LMRs (top) or these ATAC-seq peaks (APs) (bottom). Shown above each individual plot is the position weight matrix (PWM) of the enriched nucleotide sequence. The TF family that most closely matches the motif is indicated below the PWM. (
B) Heatmap depicting the percentage of ECTS-hypo-DMRs within 100 kb of ECTSGs that contain the indicated motif. Motifs that are enriched in ECTS-hypo-DMRs (
Figure 5A) are also enriched in ECTS-hypo-DMRs within 100 kb of ECTSGs. Black stars indicate statistical significance at p<1×10
−5. (
C) Heatmap depicting the percentage of ECTSAPs within 100 kb of ECTSGs that contain the indicated motif. Black stars indicate statistical significance at p<1×10
−5. (
D) ECTS-hypo-DMRs were centered on the motif for ERG, a member of the ETS family, and the frequencies of the indicated motifs were plotted as a function of distance from the ERG motif with a bin size of 1 bp. Red arrows: frequency spikes for FOX and HOX motifs are only seen in ECTS-hypo-DMRs centered on the ERG motif in lung ECs and kidney ECs, respectively. Black arrows: the sequence AGG in the TCF/LEF and ERG motifs overlap, thereby generating a frequency spike in all four EC subtypes. (
E) Heatmap depicting the percentage of ECTS-hypo-DMRs or ECTSAPs that contain the paired ETS:ZIC motif. Brain EC candidate CREs show the greatest enrichment for the paired ETS:ZIC motif relative to the other three EC subtypes. Black stars indicate statistical significance at p<1×10
−5.