Super cChIP-seq, a robust and universal epigenetic profiling method using 10 cells

ChIP-seq is the standard technique to characterize the genome-wide epigenomic modifications, which requires millions of cells as starting material. Although some methods have recently reported to be suitable for epigenomic profiling with a small number of cells, there are still no methods capable of profiling both histone modifications and DNA methylation with extremely low input. Here, we developed a new method by supplementing carrier materials of chemically modified epigenetic markers and dUPT-containing DNA fragments during ChIP procedures. Using this strategy, we generated high-quality epigenomic profiles of both histone modifications (super cChIP-seq) and DNA methylation (super cMeDIP-seq) with as few as 10 cells. Thus, we provide a robust and straightforward universal approach for epigenomic profiling starting with extremely low input. Extremely-low input ChIP-seq. Fragmentated chromatin DNA and carrier are enriched with antibody, and followed by library construction.