MobiChIP: a compatible library construction method of single-cell ChIP-seq based droplets

To illustrate epigenetic heterogeneity, versatile tools of single-cell ChIP-seq (scChIP-seq) are essential for both convenience and accuracy. We developed MobiChIP, a compatible ChIP-seq library construction method based on current sequencing platforms for single-cell applications. MobiChIP efficiently captures fragments from tagmented nuclei across various species and allows sample mixing from different tissues or species. This strategy offers robust nucleosome amplification and flexible sequencing without customized primers. MobiChIP reveals regulatory landscapes of chromatin with active (H3K27ac) and repressive (H3K27me3) histone modification in peripheral blood mononuclear cells (PBMCs) and accurately identifies epigenetic repression of the <i>Hox</i> gene cluster, outperforming ATAC-seq. Meanwhile, we also integrated scChIP-seq with scRNA-seq to further illustrate cellular genetic and epigenetic heterogeneity.