Epigenomic Landscape derived from ChIP-Seq of 1,000 mouse early embryonic cells

Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) is a powerful tool to dissect global epigenetic landscapes of cells. However, this method usually consumes millions of cells. Here we develop a robust technique for performing ChIP-Seq using as low as 1,000 cells. This method combines a semi-automatic nanoliter ChIP reaction with a carrier-based sequencing library preparation strategy without pre-amplification of the ChIP product. We used this method to investigate the pattern of trimethylation of histone 3 lysine 4 (H3K4me3) of mouse post-implantation epiblast cells at embryonic day 6.5 (E6.5) and showed that it is very similar to that of mEpiSCs. Together with the high similarity between the transcriptomes of EpiSCs and E6.5 epiblast cells, this suggests that EpiSCs is a reliable in vitro model for post-implantation epiblast cells in vivo. Overall design: Use 1 million cells mEpiSC as the positive control, 1000 mEpiSC sample is used to validate the protocol. Embryo_exp1 and embryo_exp2 are two biological replicates