Yaping Liu
Massachusetts Institute of Technology
MethylHiC reveals long-range genetic-epigenetic and epigenetic-epigenetic interactions within the same single molecule
Yaping Liu, Guoqiang Li, Bing Ren, Manolis Kellis
DNA methylation is the most extensively studied epigenetic marker that plays direct role in mammalian gene regulation, such as gene silencing and imprinting. Epigenetic gene silencing and activation has also long been envisaged as a local event. Very recent investigations indicate that large regions of chromosomes can be co-coordinately suppressed or activated. Here, we developed MethylHiC, which applies in situ Hi-C followed by bisulfite treatment to understand the long-range genetic-epigenetic and epigenetic-epigenetic interactions within the same single DNA molecule.
We validated that MethylHiC is globally consistent with both of in situ Hi-C and WGBS data generated from the same cell line. We found that DNA methylation is highly concordant at distal interacted regulatory regions within the same DNA molecule. The concordance level shows different patterns between regions at different chromatin states and imprinting regions. We also detected long-range allelic specific methylation. Further, we showed that long-range genetic-epigenetic and epigenetic-epigenetic interactions can be disrupted by Ten-eleven Translocation (TET) knockout. Moreover, by incorporating DNA methylation concordance information into the analysis, we can improve the Hi-C resolution. Our method here paves the road to evaluate the direct long-range effect of genetic and epigenetic alterations at different pathological conditions within the same DNA molecule.
