GSE113818
Genome-wide maps of histone modifications in endometrial cancer cell lines
DNA regulatory elements are reported to be enriched for variants identified by genome-wide association studies to be significantly assocaited with risk of complext traits. Here, we have performed genome-wide mapping of histone modifications in two endometrial cancer cell lines and performed interestions of these sites with genetic risk variants identified by genome-wide association study of endometrial cancer. Histone modifications indicative of enhancers (H3K4Me1 and H3K27Ac) and promoters (H3K27Ac and H3K4Me3) were identified by ChIP-seq in Ishikawa and JHUEM-14 cells, pre- and post-stimulation by estrogen. Overall, 73% of endometrial cancer genetic risk variants overlapped at least histone modification site. This overlap was significantly greater than the overlap observed for these histone marks with genetic risk variants related to, for example, endometriosis (51%; Fisher's Exact p = 8.7x10-8) or schizophrenia (40%; Fisher's Exact p < 2.2x10-16). These findings indicate the relevance of the selected cell and tissue types for informing endometrial cancer biology. Overlaps between genetic risk variants and histone modification sites increased significantly after stimulation with estrogen (50% versus 38% for unstimulated features; Fisher's Exact p = 5.6x10-3), emphasizing the importance of estrogen in endometrial cancer aetiology. Overall design: ChIP-seq of 3 different histone modifications in 2 endometrial cancer cell lines, before and after estrogen stimulation