library_construction_protocol: ATAC-seq was performed on 50,000 K562 cells with all buffer compositions and reaction conditions following the published Omni-ATAC protocol (Corces et al., 2017) unless otherwise specified. Briefly, cells were pelleted, washed once with ice-cold PBS, resuspended in ice-cold Lysis Buffer, and incubated on ice for 3 min. Upon addition of Wash Buffer and gentle inversion, nuclei were pelleted, and supernatant (cytoplasm) was discarded. Nuclei were then resuspended gently in 50 μL transposition reaction mix containing 1 μL homemade Tn5 transposase and incubated at 37°C for 30 min with 1000 rpm shaking. DNA was purified using the MinElute PCR purification kit (Qiagen) and eluted in 21 μL volume. The entire purified product (~20 μL) was mixed with 2.5 μL of each Nextera index primer (25 μM) and 25 μL NEBNext High-Fidelity 2X PCR Master Mix and subjected to a first round of PCR: initial extension 72°C for 5 min; initial denaturation 98°C 30s; 5 cycles of 98°C for 10 s, 63°C for 30 s, 72°C for 1 min. To determine additional cycles needed to avoid over-amplification, a qPCR analysis was performed using 5 μL of the first-round PCR reaction (Buenrostro et al., 2015). For all ATAC-seq libraries, 3~4 additional cycles of amplification were performed on the remaining 45 μL PCR reaction, followed by sequential cleanup using the MinElute PCR purification kit (Qiagen) and homebrew SPRI beads (1.5× bead ratio). DNA concentration was measured by the Qubit dsDNA High Sensitivity assay (Thermo Fisher). The libraries were pooled for sequencing on the Element Biosciences AVITI (2 × 80 bp paired-end sequencing) or Illumina NovaSeq X Plus platform (2 × 150 bp paired-end sequencing).