aFARP-ChIP-seq, a convenient and reliable method for genome profiling in as few as 100 cells with a capability for multiplexing ChIP-seq.

Much effort has been devoted to understand how chromatin modification regulates development and disease. Despite recent progress, however, it remains difficult to obtain high-quality epigenomic maps using chromatin-immunoprecipitation-coupled deep sequencing (ChIP-seq) in samples with low-cell numbers. Here, we present an Atlantis dsDNase-based technology, aFARP-ChIP-seq, that provides accurate profiling of genome-wide histone modifications in as few as 100 cells. By mapping histone lysine trimethylation (H3K4me3) and acetylation (H3K27Ac) in group I innate lymphoid cells (ILC1) sorted from different tissues in parallel, aFARP-ChIP-seq uncovers putative active promoter and enhancer landscapes of several tissue-specific Natural Killer cells (NK) and ILC1. aFARP-ChIP-seq is also highly effective in mapping transcription factor binding sites in small number of cells. Thus, aFARP-ChIP-seq offers multiplexing mapping of both epigenome and transcription factor binding sites using a small number of cells.