library_construction_protocol: CUT&RUN experiments were carried out following Epicypher CUT&RUN protocol (version 1.6, August 2020) with minor modifications. Briefly, nuclei from 5x105 cells were isolated with wash buffer (20 mM HEPES-KOH, pH 7.5, 150 mM NaCl, 0.5 mM Spermidine, and 1x protease inhibitor cocktails from Sigma), captured with Concanavalin A conjugated paramagnetic beads (Bangs Laboratory Inc.) and incubated while nutating with 0.5 µl primary antibody for EZH2 (Cell Signaling Technology), or SUZ12 (Cell Signaling Technology) in antibody buffer (20 mM HEPES-KOH, pH 7.5, 150 mM NaCl, 0.5 mM Spermidine, 0.02% digitonin, 2 mM EDTA and 1x protease inhibitor cocktails from Sigma) overnight. After washing with digitonin buffer (20 mM HEPES-KOH, pH 7.5, 150 mM NaCl, 0.5 mM Spermidine, 0.02% digitonin and 1x protease inhibitor cocktails from Sigma), pAG-MNase (Epicypher Inc) was added at a 1:20 ratio and incubated for 10 min at RT. The nuclei were washed again and placed on ice. To activate pAG-MNase, CaCl2 was added to a final concentration of 2 mM. The reaction was inubated for 2 hours while nutating at 4°C and stopped by addition of STOP buffer (340 mM NaCl, 20 mM EDTA, 4 mM EGTA, 50 mg/mL RNase A and 40 mg/mL glycogen). The protein-DNA complex was released by incubating for 10 min at 37°C. DNA was extracted using Qiagen Minelute PCR purification kit. Purified DNA was used for library preparation. CUT&RUN libraries were prepared using the Illumina NEBNext Ultra II ChIP-Seq sample kit, according to the manufacturer's protocol. Libraries were validated using the Agilent Technologies 2100 Bioanalyzer