library_construction_protocol: ESCs were spiked with 2% of human cells (HeLa), then cross-linked in 1% formaldehyde/PBS for 10min at room temperature. After quenching with 125mM glycine for 5min at room temperature, followed by 15min at 4°C, cells were washed in cold PBS and stored at −80°C. Cells were diluted at 5 million cells per 100μl in shearing buffer (1% SDS, 10mM EDTA, 50mM Tris-HCl pH8.0, 5mM NaF, Halt™ Protease Inhibitor Cocktail (Thermo Fisher), 1mM PMSF), rotating at 4°C for 30min, then 100μl lysate was passed into a microTUBE AFA Fiber Snap-Cap (Covaris). Chromatin was sheared to 200–500 bp fragments on a Covaris E220 with settings PIP 175, Duty 10%, CPB 200, for 7 minutes. Supernantants were pooled by condition, and immunoprecipitation was performed overnight using 200μl of lysate (~chromatin from 10 million cells) and 5µg of antibody (Proteintech 15073-1-AP), following the iDeal ChIP-seq kit for Transcription Factors (Diagenode) protocol. Elution, de-crosslinking, and DNA purification were performed per manufacturer's instructions. Libraries were constructed from ~2ng DNA and prepared using the NEBNext Ultra II DNA Library Prep Kit for Illumina (NEB).