EpiMethylTag simultaneously detects ATAC-seq or ChIP-seq signals with DNA methylation

Abstract

Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. We developed a low input, low sequencing depth method, EpiMethylTag that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.

CUT&Tag-BS: an efficient and low-cost method for simultaneous profiling of histone modification and DNA methylation

“…CUT&Tag-BS overcomes some of the limitations of existing methods. First, CUT&Tag-BS uses native cells without formaldehyde fixation thus avoiding the side effects of crosslinking/decrosslinking, as reflected by high bisulfite conversion efficiency (99.5%) and improved overall alignment rate in CUT&Tag-BS (~80%) (Figure 2A) compared with EpiMethylTag (~65%) and ChIP-BS-seq (~33%) (Lhoumaud et al, 2019). Second, CUT&Tag-BS adopts a tagmentation-based bisulfite sequencing library preparation strategy, which is faster and requires substantially less DNA than conventional ligation-based bisulfite sequencing library construction (Wang et al, 2013).…”

“…Those two methods use a ligation-based bisulfite sequencing library preparation strategy, which requires a large amount of ChIP-ed DNA (~ 100 ng); thus, they are not suitable for low-input samples. To reduce the amount of ChIP-ed DNA required, EpiMethylTag (Lhoumaud et al, 2019) was developed recently using tagmentaion-based library preparation strategy instead. Despite the differences in library construction, the three methods all rely on crosslinked ChIP to capture chromatin fragments associated with protein of interest.…”