Figure 5: Functional mapping of 9p21.3 locus identifies AP-1- and TCF21-dependent regulatory mechanisms.
From: Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci
(a) UCSC browser screenshot at 9p21.3/CDKN2B-AS locus, showing overlap of candidate SNP rs1537373 with ATAC-seq open chromatin tracks in coronary tissue (n=3 biological replicates per condition) and HCASMCs treated under various conditions (n=2 biological replicates per condition), TF-binding ChIP-seq tracks for TCF21, JUN and JUND, and active enhancer histone modification H3K27ac ChIP-seq (n=4 biological replicates), as well as ENCODE layered H3K27ac for HUVEC (blue) and NHLF cells (purple). Inset, motifs generated from HOMER in open chromatin regions showing alignment to reference sequence and position relative to rs1537373 SNP. Genomic coordinates refer to hg19 assembly. (b) Normalized ATAC-seq read counts for HCASMCs treated under various conditions and by genotype at rs1537373. Values represent mean±s.e.m. (n=2 biological replicates for stimulations and n=5 biological replicates for different genotypes). (c) Allele-specific ChIP (haploChIP) for AP-1 proteins (JUN, JUNB and ATF3), TCF21 and H3K27ac in HCASMCs heterozygous at rs1537373. Values represent mean±s.e.m. of triplicates from a representative experiment (n=5 biological replicates). *P<0.01 versus control, IgG or between two genotypes using an unpaired two-tailed t-test with Welch’s correction for unequal variances.
