Fig. 5: rtQTLs affect replication timing by altering TF binding motifs.

a, b Binding of TFs such as OCT4 and NANOG promotes earlier replication, while binding of CTCF, REST and other factors is associated with later replication in hESCs (a) and iPSCs (b). Chi-squared test, FDR <10%. c Examples of rtQTLs altering binding affinity of TFs that function as replication activators or repressors. Heterozygous profiles are not plotted. Center panels: ChIP-seq tracks. Lower panels: sequence logos of the motifs containing the rtQTL SNPs, motif names, and changes in binding affinity (calculated based on motif scores). Asterisk indicates that the motif was on the negative strand and the sequence shown is the reverse complement. Red arrows: locations of the rtQTL SNPs. For activators, the rtQTL allele associated with early replication encodes an intact binding motif, while the allele associated with late replication abolishes the motif. Repressors have the opposite pattern: the early allele abolishes the motif.