Figure 3.
Example of association between a TF binding affinity CRM variant and gene expression. (A) Genome browser representation of the distal interactions (pink arches) of KLF6 promoter in the LCL GM12878, as detected by PCHi-C (49). Two out of the three fragments interacting with KLF6 promoter are shown; the third fragment, which is located 850 kb away from the KLF6 promoter and contains the gene LINC00705, was omitted due to space constraints. The chromHMM genome segmentation tracks for GM12878 are shown immediately below (80). CRMs at the two distally interacting fragments and the TSS-proximal window are depicted in azure blue. The rightmost CRM, which interacts with the KLF6 promoter 88 kb away, is predicted to impact BATF binding affinity across the 359 LCLs. (B) Box plot showing the association between mRNA levels (as measured with RNA-seq by the GEUVADIS consortium) and predicted CRM haplotype with respect to BATF binding affinity in LCLs. KLF6 expression is significantly associated with BATF binding type (gene-level FDR adjusted P-value = 1.21 × 10−2, BATF variant P-value = 5.16 × 10−4, effect size = 0.26).