Multiplexed and ultralow-input ChIP-seq enabled by tagmentation-based indexing and facile microfluidics

Epigenome constitutes an important layer that regulates gene expression and dynamics during development and diseases. Extensive efforts have been made to develop epigenome profiling methods using a low number of cells and with high throughput. Chromatin immunoprecipitation (ChIP) is the most important approach for profiling genome-wide epigenetic changes such as histone modifications. In this report, we demonstrate microfluidic ChIPmentation (mu-CM), a microfluidic technology that enables profiling cell samples that individually do not generate enough ChIP DNA for sequencing library preparation. We used a simple microfluidic device to allow 8 samples to be processed simultaneously. The samples were indexed differently using a tagmentation-based approach (ChIPmentation) and then merged for library preparation. Histone modification profile for each individual sample was obtained by demultiplexing the sequencing reads based on the indexes. Our technology allowed profiling 20 cells and is well suited for cell-type-specific studies using low-abundance tissues. Overall design: We profiled H3K4me3 of GM12878 cell line starting with 100 cells down to as few as 20 cells per assay. We also examined H3K4me1 with 1,000 GM cells. We developed a tagmentation-based microfluidic method, which performed 8 replicate experiments in parallel. The file name contains information on the histone modification type, the number of cells per unit, and the number of the unit. For example, "H3K4me3-100-1" refers to the data set on H3K4me3 using 100 cells per assay/unit produced by unit 1 of the 8-unit microfluidic device.