Single cell chromatin immunocleavage sequencing (scChIC-Seq) to profile histone modification

We report a single-cell chromatin immunocleavage sequencing (scChIC-seq) methodology for analyzing histone modifications, which involves targeting of the micrococcal nuclease (MNase) by tethering it to an antibody and selective PCR amplification of cleaved target sites. We show that the protocol reliably detects the H3K4me3 and H3K27me3 target sites in single human white blood cells (WBC), resulting data for successful identification of unique blood cell types based on clustering analysis. Overall design: The technique, scChIC-seq, was applied to profile H3K4me3 and H3K27me3 using small number of cells and single cells. By comparing with the Bulk ChIP-seq signal, scChIC-seq was shown to have high specificity. scChIC-seq was applied to profile H3K4me3 using single human white blood cells. The highly co-methylated and highly variable peaks were shown to be related to underlying cellular populations.