DMF-ChIP-seq for Highly Sensitive and Integrated Epigenomic Profiling of Low-Input Cells

Mapping genome-wide DNA–protein interactions (DPIs)
provides
insights into the epigenetic landscape of complex biological systems
and elucidates the mechanisms of epigenetic regulation in biological
progress. However, current technologies in DPI profiling still suffer
from high cell demands, low detection sensitivity, and large reagent
consumption. To address these problems, we developed DMF-ChIP-seq
that builds on digital microfluidic (DMF) technology to profile genome-wide
DPIs in a highly efficient, cost-effective, and user-friendly way.
The entire workflow including cell pretreatment, antibody recognition,
pA-Tn5 tagmentation, fragment enrichment, and PCR amplification is
programmatically manipulated on a single chip. Leveraging closed submicroliter
reaction volumes and a superhydrophobic interface, DMF-ChIP-seq presented
higher sensitivity in peak enrichment than other current methods,
with high accuracy (Pearson Correlation Coefficient (PCC) > 0.86)
and high repeatability (PCC > 0.92). Furthermore, DMF-ChIP-seq
was
capable of processing the samples with as few as 8 cells while maintaining
a high signal-to-noise ratio. By applying DMF-ChIP-seq, H3K27ac histone
modification of early embryonic cells during differentiation was profiled
for the investigation of epigenomic landscape dynamics. With the benefits
of high efficiency and sensitivity in DPI analysis, the system provides
great promise in studying epigenetic regulation during various biological
processes.