In order to illustrate the epigenetic heterogeneity, versatile tools of single-cell ChIP-seq (scChIP-seq) are necessary to meet the convenience and accuracy. Here, we develop MobiChIP, a compatible ChIP-seq library construction method based current sequencing platform with single cell level. As a novel capture strategy, MobiChIP is efficient to capture the fragments from tagmented nuclei of numerous species and execute the mixing of samples from different tissues or species. Especially, this strategy enables the flexible sequencing manipulation and sufficient nucleosome amplification without customized sequencing primers. MobiChIP reveals the landscape of chromatin regulation regions with active (H3K27ac) and repressive (H3K27me3) histone modification markers in peripheral blood mononuclear cells (PBMCs), and accurately unveiled the epigenetic repression of hox gene cluster in PBMCs than ATAC-seq. Meanwhile, we complete the bioinformatics pipeline to integrates the scChIP-seq data and scRNA-seq to illustrate the cellular epigenetic and genetic heterogeneity.

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