Visualization of DNA elements in the rs2241423-associated haplotype block utilizing ENCODE. The haplotype block containing rs2214123 was visualized employing ENCODE (ENCyclopedia Of DNA Elements) data tracks via the UCSC genome browser (http://genome.ucsc.edu/ webcite). We chose to visualize regulatory binding sites generated from transcription factor chromatin-immunoprecipitation assays followed by sequencing (ChIP-seq), histone modifications, DNaseI hypersensitivity clusters, as well as mammalian conservation. Rs2214123 was found to be located in close proximity to a number of potential regulatory sites. The closest cluster was found only 400 bases downstream of rs2241423. Among the DNA-interacting transcription factors identified as binding to this site, early growth response protein 1 (EGR1) gave the strongest signal for occupancy. In addition, this site also overlaps with a signal peak for monomethylation of lysine 4 on histone H3 (H3K4Me1), as identified by ChIP-seq in K526 cells, a human erythroleukemia cell line, as well as DNAseI activity which indicates chromatin modifications consistent with a regulatory element at this position. An additional cluster of regulatory elements was identified approximately 10 kb upstream of rs2241423 exhibiting strong signals for H3K4Me1 in several cell lines as well as for lysine 27 acetylated histone H3, an indicator of active regulatory elements. This site also overlaps with strong signals for DNaseI hypersensitivity clusters which are characteristic of cis-regulatory elements. DNA from this cluster was found to co-precipitate with antibodies for several different transcription factors, strong signals for occupancy in this cluster were observed for transcription factor 12 (TCF12) and cMyc.
Rask-Andersen et al. BMC Medical Genetics 2012 13:36 doi:10.1186/1471-2350-13-36