DMF-ChIP-seq for\nHighly Sensitive and Integrated Epigenomic\nProfiling of Low-Input Cells

Mapping genome-wide DNA–protein interactions (DPIs)\nprovides\ninsights into the epigenetic landscape of complex biological systems\nand elucidates the mechanisms of epigenetic regulation in biological\nprogress. However, current technologies in DPI profiling still suffer\nfrom high cell demands, low detection sensitivity, and large reagent\nconsumption. To address these problems, we developed DMF-ChIP-seq\nthat builds on digital microfluidic (DMF) technology to profile genome-wide\nDPIs in a highly efficient, cost-effective, and user-friendly way.\nThe entire workflow including cell pretreatment, antibody recognition,\npA-Tn5 tagmentation, fragment enrichment, and PCR amplification is\nprogrammatically manipulated on a single chip. Leveraging closed submicroliter\nreaction volumes and a superhydrophobic interface, DMF-ChIP-seq presented\nhigher sensitivity in peak enrichment than other current methods,\nwith high accuracy (Pearson Correlation Coefficient (PCC) > 0.86)\nand high repeatability (PCC > 0.92). Furthermore, DMF-ChIP-seq\nwas\ncapable of processing the samples with as few as 8 cells while maintaining\na high signal-to-noise ratio. By applying DMF-ChIP-seq, H3K27ac histone\nmodification of early embryonic cells during differentiation was profiled\nfor the investigation of epigenomic landscape dynamics. With the benefits\nof high efficiency and sensitivity in DPI analysis, the system provides\ngreat promise in studying epigenetic regulation during various biological\nprocesses.