GSE68858
Three-dimensional analysis of regulatory features reveals functional enhancer-associated loops
To gain insight into the relationship between chromatin structure and gene expression, we conducted a Tethered Chromatin Capture (TCC) analysis using MCF7 breast cancer and PANC1 pancreatic cancer cells. We applied a novel Hi-C analysis algorithm and identified hundreds of thousands of Interacting Loci Pairs (ILPs) in each of the two cell types. We classified ILPs according to location with respect to gene structure, gene expression, different histone modifications, DNase hypersensitivity, and RNA polymerase II and CTCF binding, identifying distinct classes of ILPs. Interestingly, we found that only 5% of the ILPs involved promoter regions, with even fewer promoter-enhancer loops. We find that genes associated with promoter-enhancer loops have cell type-specific functional annotations. We then tested the impact of pharmacological inhibition of histone acetylation on genes having promoter-enhancer ILPs in PANC1 cells. We found that genes with promoter-enhancer ILPs show reduced expression in response to drug treatment, suggesting that the chromatin loops we identified are functional. Overall design: We analyzed two datasets, TCC in MCF7 and PANC1 cells. We then correlated them with histone modification data and gene expression data.  Anti-CTCF ChIP-Seq was performed on PANC1 cells.