library_construction_protocol: Cells were first crosslinked with 2 mM disuccinimidyl glutarate (Santa Cruz) at room temperature for 30 min, washed 3 times with PBS and then crosslinked with 1% formaldehyde at room temperature for 5 min before quenching with 200 mM glycine at room temperature for 5 min. Two additional PBS washes were performed, and cell pellets were lysed with Farnham Lysis Buffer (5 mM PIPES, pH 8, 85 mM KCl, 0.5% NP40, 10 mM glycine, 1× Thermo Scientific Pierce Protease Inhibitor) on ice for 20 min. After centrifugation and supernatant removal, the nuclear pellet was resuspended in RIPA Lysis Buffer (10 mM Tris-HCl, pH 8, 150 mM NaCl, 1 mM EDTA, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, 1× Thermo Scientific Pierce Protease Inhibitor) and incubated on ice for 10 min. Sonication was carried out using a Diagenode Bioruptor device at High Setting, 30 sec on/30 sec off for three rounds of 10-min cycle to shear chromatin to a size of 100~300 bp. The lysate was then clarified by centrifugation at 20,000 r.c.f., 4°C for 15 min, of which 2% was kept as ChIP input. Each IP used 4 million cells/4 µg antibody/40 µL Dynabeads Protein G (Thermo Scientific). Beads were washed three times with 5 mg/mL BSA in PBS and incubated with corresponding antibodies at 4°C for 6 h to overnight with rotation. Another three BSA/PBS washes were performed to remove unbound antibodies, and the clarified chromatin lysate was added to the beads and incubated overnight at 4°C with rotation. Beads were then washed with the following buffers, each for three times: Low Salt Wash Buffer (20 mM Tri-HCl, pH 8, 2 mM EDTA, 150 mM NaCl, 1% Triton X-100, 0.1% SDS), High Salt Wash Buffer (20 mM Tri-HCl, pH 8, 2 mM EDTA, 500 mM NaCl, 1% Triton X-100, 0.1% SDS), and LiCl Wash Buffer (10 mM Tri-HCl, pH 8, 1 mM EDTA, 250 mM LiCl, 1% NP-40, 1% sodium deoxycholate). After one final wash with TE Buffer (10 mM Tris-Cl, pH 8, 1 mM EDTA), chromatin was eluted from beads by two rounds of incubation with ChIP elution buffer (1% SDS, 0.1 M sodium bicarbonate). Each incubation involved 15 min shaking at 1200 rpm at 65°C, followed by 15 min rotation at room temperature. The eluates and input samples were treated with RNase A at 37°C for 30 min, de-crosslinked at 65°C overnight with 900 rpm shaking, followed by Proteinase K treatment at 45°C for 2 h with shaking. DNA was purified using MinElute PCR Purification Kit (Qiagen). For p300 ChIP, sequencing libraries were prepared using a Tn5 tagmentation-based protocol. Briefly, 20 μL tagmentation reactions were set up with 0.35 ng of ChIP DNA or 1 ng of input DNA, 1× TAPS-DMF Buffer (10 mM TAPS-NaOH, pH 8.5, 5 mM MgCl2, 10% DMF), and 1 μL of 1:15 diluted homemade Tn5 transposase (a kind gift from Dr. Roman Spektor). The reaction was incubated at 55°C for 10 min, and 2 μL of 1% SDS was added immediately, followed by another 55°C incubation for 7 min to strip off Tn5 from DNA. Post-tagmentation PCR was carried out in 100 μL volume with 10 μL of the tagmentation reaction, 1× Phusion HF Buffer, 200 μM dNTPs, 400 nM of each Illumina Nextera index primer, and 1 μL of homemade Phusion polymerase. The PCR program was: initial extension 72°C for 3 min; initial denaturation 98°C 30s; 13 cycles of 98°C for 10 s, 63°C for 30 s, 72°C for 3 min; and final extension 72°C for 5 min. PCR products were purified first using the MinElute PCR purification kit (Qiagen), followed by an additional cleanup with homemade SPRI beads (1.5× bead ratio) to ensure complete removal of unused primers. DNA concentration was measured by the Qubit dsDNA High Sensitivity assay (Thermo Fisher). The libraries were pooled for sequencing on the Element Biosciences AVITI platform (2 × 80 bp paired-end sequencing).