Fig. 5: Distinctive CPD damage signatures at NF-Y and ETS binding sites in the DPH3 promoter.

a Overview of the DPH3/OXNAD1 bidirectional promoter (−2000 to +1000 bp relative the DPH3 TSS), including Capture CPD-seq UV footprinting signals and regulatory features. Predicted binding sites (sequence motif matches) for NF-Y (CCAAT) and ETS (TTCC[T/G]) are shown together with ENCODE DNase I and ChIP signals for NF-YA/NF-YB and ETS (ELK4/ELK1). Per-base CPD damage changes in cellular vs. naked samples are shown as log₂ ratios (+4 = 16-fold increase; −4 = 16-fold decrease) together with associated P-values (uncorrected from two-sided negative binomial test). CPD-based prediction of bound/unbound status for motif sites is indicated in black/gray, respectively (see Supplementary Fig. 10 for details). b Closeup view of region “2” indicated in Fig. 5a. ChIP-supported NF-Y sites in this region exhibit a distinctive CPD damage signature involving strong stimulation of damage (up 6.7-fold) at the center of the motif. Each bar refers to one diPy (only one strand can contain a diPy at each position). c Example of an unbound NF-Y site (region “3” in Fig. 5a). d Closeup view of a promoter-proximal ETS site in DPH3 (region “1”). Strongly elevated CPD damage at this site (17.2-fold increase in cell relative naked DNA) coincides at base-level with a prominent somatic mutation hotspot in melanoma (mutation counts based on 221 melanoma whole genome sequences is indicated). DNase I footprints from Vierstra, et al.³¹ are indicated as green lines in b–d. Source data are provided as a Source Data file.