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

Abstract

Much effort has been devoted to understand how chromatin modification regulates development and disease. Despite recent progress, however, it remains difficult to achieve high sensitivity and reliability of chromatin-immunoprecipitation-coupled deep sequencing (ChIP-seq) to map the epigenome and global transcription factor binding sites in cell populations of low cell abundance. We present a new 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 H3K27Ac in group I innate lymphoid cells from different tissues, aFARP-ChIP-seq uncovers potentially distinct active promoter and enhancer landscapes of several tissue-specific NK and ILC1. aFARP-ChIP-seq is also highly effective in mapping transcription factor binding sites in small number of cells. Since aFARP-ChIP-seq offers reproducible DNA fragmentation, it should allow multiplexing ChIP-seq of both histone modifications and transcription factor binding sites for low cell samples.