Profiling chromatin state by single-cell itChIP-seq [sonication ChIP]

We present a low-cost, generalizable ChIP-seq (itChIP), compatible to both low-input and single cells for profiling chromatin states. This method combines chromatin opening, simultaneous cellular indexing and chromatin tagmentation in a single tube. Single-cell itChIP data yield ~ 5000 unique reads per cell, sufficiently defining cell identifies and subpopulations of a given cell type. Our results demonstrate that itChIP is a generalizable technology for single-cell chromatin profiling of samples limited to ultra-low number of cells. Sonication-based ChIP was the traditional method to profile modification of chromatin. Chromatin was sonicated by Q800R to 200-800 bp fragments. After being pulled down by antibody and Dynabeads protein A beads, fragments were ligated with adaptors by ChIPmentation method. After being amplified, libraries were sequenced on Illumina HiSeq 4000 for paired end 150 bp. Sonication-ChIP data played as the positive control of our itChIP-seq.