library_construction_protocol: The 4f-SAMMY-seq  fractionation was performed on 250.000 MEFs. Cells were washed twice in cold PBS and resuspended in 600 μL of cold cytoskeleton-Triton buffer (CSK-Triton buffer: 10 mM PIPES pH 6.8, 100 mM NaCl, 1 mM EGTA, 300 mM Sucrose, 3 mM MgCl2, 1mM PMSF, Protease Inhibitor Cocktail Roche 04693116001, 1 mM DTT, 0.5% Triton X-100). After 10 minutes on a rotator at 4°C, samples were centrifugated for 3 minutes at 900g at 4°C and the cytoskeletal structure were collected as S1 fraction. Pellets were then washed for 10 minutes on the rotator at 4°C with an additional volume of the CSK-Triton buffer, resuspended in 100 μL of cytoskeleton buffer (CSK buffer: 10 mM PIPES pH 6.8, 100 mM NaCl, 1 mM EGTA, 300 mM Sucrose, 3 mM MgCl2, 1mM PMSF, 1X Protease Inhibitor Cocktail Roche 04693116001) and incubated with 6 U of DNase I (Invitrogen, AM2222) for 60 min at 37°C. To stop digestion, ammonium sulphate was added in the CSK buffer to a final concentration of 250 mM. After 5 min on ice, samples were pelleted at 900g for 3 min at 4°C and the supernatant, containing digested chromatin fragments, was collected as S2 fraction. The pellet was then washed with 200 μL of CSK buffer and pelleted at 3000g for 3 min at 4°C. Afterwards, the pellet was resuspended in 100 μL of CSK-NaCl buffer (10 mM PIPES pH 6.8, 2 M NaCl, 1 mM EGTA, 300 mM Sucrose, 3 mM MgCl2, 1mM PMSF, 1X Protease Inhibitor Cocktail Roche 04693116001), incubated 10 min on a rotator at 4°C, centrifuged at 3000g 3 min at 4°C and the supernatant was conserved as S3 fraction. Finally, after two washes in 200 μL of CSK-NaCl buffer, pellets were solubilized in in 8M urea for 10 minutes at RT and the final suspension was labelled as S4 The libraries for SAMMY-seq were generated using the NEBNext Ultra II DNA Library Prep Kit for Illumina (NEB, BE7645L) and the NEBNext Multiplex Oligos for Illumina (NEB, BE6440S).