library_construction_protocol: 5X106 cells were crosslinked using formaldehyde (1% final concentration) for 10 min at RT. The reaction was quenched using glycine (130 mM final concentration). After a PBS wash, the cell pellets were frozen and stored at -80°C. Cells were resuspended in ice-cold lysis buffer (10 mM Tris-HCl pH 8.0, 10 mM NaCl, 0.2 % NP-40) with protease inhibitors (Thermo Scientific) and incubated on ice for 15 min. The lysate was homogenized using dounce homogenization and nuclei were pelleted at 2,500 xg at RT. The nuclei were then washed with and resuspended in ice-cold NEBuffer 3.1 (NEB). SDS was then added (0.1% final concentration) and the nuclei were incubated at 65°C for 10 min. SDS was quenched by adding Triton X-100 (1% final concentration). DpnII (50,000 U, NEB) was added, and chromatin digestion was carried out overnight at 37°C. End repair was performed at 23°C for 5 hr using Klenow Fragment (3'→5' exo-, 50 U, NEB), NEBuffer 3.1 (0.112 X), 28 nM of each dCTP, dGTP. dTTP, and biotin-14-dATP. Blunt ligation was performed at 16°C for 4 hr using T4 DNA ligase (60 U, Invitrogen) and ligation buffer (1X, Invitrogen), Triton X-100 (1%) and BSA (1 mg/mL). Crosslinks were reversed at 65°C overnight, and protein was degraded using proteinase K. The DNA was extracted using phenol-chloroform (Invitrogen). Biotin removal from unligated ends was performed at 20°C for 4 hr using 5 µg of DNA, 5 U T4 DNA Pol, NEBuffer 2.1 (1X, NEB), 25 nM dATP, and 25 nM dGTP. DNA was sheared to obtain 200-300 bp fragments sizes using a sonicator (Covaris). DNA size fractionation was performed using AMPure XP magnetic beads (Beckman Coulter) as described by the manufacturer. End repair was performed at 20°C for 30 min using 50 µL of size-selected DNA elute, T4 DNA pol (7.5 U, NEB), T4 polynucleotide kinase (25 U, NEB), Klenow DNA pol (2.5 U, NEB), ligation buffer (1X, NEB). Biotin DNA pulldown was performed using 1 µg of end-repaired DNA, MyOne streptavidin C1-coated beads (Invitrogen), according to manufacturer instructions. The beads were resuspended in 41 µL TE. A-tailing was then performed at 37°C for 30 min, followed by addition of Klenow fragment (3' -> 5' exo-, 15 U, NEB), dATP (0.2 nM), and NEBuffer 2.1 (1X). After a wash with ligation buffer, the beads were resuspended in 36.25 µL ligation buffer. Adapter ligation was then performed at RT for 2 hr with the addition of T4 ligase (4 U), ATP (0.2 mM), paired ended adapters (5 µL of 15 µM annealed adapters, 5' ligation buffer (2.75 µL). After washing twice with tween wash buffer (TWB; 5 mM Tris-HCl [pH=8.0], 0.5 mM EDTA, 1 M NaCl, 0.05% Tween), the beads were resuspended in Binding Buffer (10 mM Tris-HCl pH 8.0, 1 mM EDTA, 2 M NaCl). Following a wash with NEBuffer 2.1, beads were resuspended in 20 µL of NEBuffer 2.1. The library of ligated fragments was then PCR amplified for 6 cycles using 6 µL of beads, 2 µL of 10 µM adapter primers (G19-PE Primer 1.0 and 2.0), 25mM dNTPs, 10X PfU buffer, and 2 µL PfuUltra in a 30 µL reaction and the following conditions: 98°C for 3 min, 5 cycles of: 98°C for 20 sec, 60°C for 30 sec, and 72°C; and a final amplification at 72°C for 5 min. Finally, the PCR products were combined, and primer dimers were removed using AMPure XP beads.