library_construction_protocol: ~10^8 cells were washed twice by 50 mM EDTA (pH 8.0) and embedded in 0.75% low melting agarose plugs with Lyticase (1 mg/ml, final concentration). Plugs were then treated with Lyticase and Lysing (1 mg/ml, final concentration, 37˚C for 1.5 hours), Proteinase K (50˚C for 2 hours, followed by 37˚C for 7 hours) and RNase A (37˚C for 1 hour) in turn. DNA ends within plugs were either not trimmed (native END-seq) or trimmed (typical END-seq) with Exonuclease T and Exonuclease VII. All samples were followed by A-tailing with Klenow fragment exo- to ligate with 3' T overhang of biotinylated hairpin adaptors (introducing Illumina p5 primers). After plug melting and sonication, DNA fragments were sheared to 300-500 bp in length and precipitated by ethanol, dissolved in 10 mM  Tris, pH 8.0. Extract DNA from plugs are enriched by streptavidin beads. End-repair by T4 DNA polymerase, Klenow fragment and T4 polynucleotide kinase was performed before second A-tailing with Klenow fragment exo-, allowing the ligation of distal hairpin adaptors with p7 Illumina primers. Finally, after USER enzyme digestion, libraries were PCR amplified and selected by AMPure XP beads for Illumina sequencing.