Figure 2. Allele-specific binding of FOXA1 at the rs4442975 site.

(a) Epigenetic and transcriptional landscape of the 2q35 risk interval. Coloured histogram denotes histone modification ChIP-seq data from ENCODE. Data from the UCSC Genome Browser, including epigenetic marks for H3K4me1 in seven cell types from ENCODE²⁸, H3K4me2 from MCF7 cells⁴, DNaseI hypersensitivity clusters in 125 cell types from ENCODE²⁸, and TF ChIP-seq data from MCF7 and T47D ER+ breast cancer cells, which are homozygous for the g-allele of rs4442975 and rs6721996 (ENCODE). The PRE contains SNP rs4442975. (b) Position weight matrix of FOXA1 from JASPAR, with homology to the risk (g) and cancer-protective (t) alleles of rs4442975 coloured below. (c) IGR histogram for SNP rs4442975 predicting the binding intensity of FOXA1 using a seven-nucleotide affinity model⁵. The top row of coloured numbers shows the number of instances for each K-mer found genome wide within H3K4me2 elements in MCF7 cells. The bottom row shows the averaged binding intensities at the K-mers (50 bp window). Control profiles, shown in grey, are generated by scrambling the probed sequence. (d) Allele-specific FOXA1 ChIP-qPCR results assessed at the rs4442975 SNP in heterozygous BT474 breast cancer cells. Error bars denote s.d. P values were determined with a two-tailed t-test. **P<0.01.