Native MOWChIP-seq: Genome-wide profiles of key protein bindings reveal functional differences among various brain regions

Here we developed a low-input ChIP-seq technology and associated protocol for profiling RNA Polymerase II, transcription factor, or enzyme binding at the genome scale. The new approach, termed native MOWChIP-seq or nMOWChIP-seq, produces genome-wide binding profiles using as few as 1000 cells. We show that MNase digestion is effective for preserving the links between protein and genome and facilitating low-input profiling. We show that native MOWChIP-seq is universally effective for profiling genome-wide protein bindings. We generated high-quality ChIP-seq data using as few as 1,000 GM12878 cells for studying RNA Pol II, 5,000 cells for TF EGR1, and 10,000 cells for HDAC2. We applied this method to study genome-wide binding of RNA Pol II, EGR1 and MEF2C in two functional regions of the mouse brain: prefrontal cortex (PFC) and cerebellum. The filename contains information on the nature of sample (GM12878 cell line, mouse PFC, mouse cerebellum), the target being profiled, number of cell/nuclei used per assay, special condition of the sample, and replicate number. 2 technical replicates were conducted each sample. For example, "GM12878-Pol2-S5-10K-1" refers to technical replicate 1 of the assay using 10,000 GM12878 cells, profiling Pol2 (S5).