library_construction_protocol: For H3K4me3 HiChIP, 10 million formaldehyde crosslinked cells per condition in biological replicates were used. HiChIP was performed as described before (Mumbach et al., 2016). In our experiments, 375 U of MboI (NEB, R0147M) restriction enzyme was used for chromatin digestion. Shearing was performed in three Covaris microtubes per sample and using the following parameters on a Covaris E220 (Fill Level = 6, Duty Cycle = 5, PIP = 140, Cycles/Burst = 200, Time = 200s). H3K4me3 IP was performed using 7.5 μg of antibody (Millipore, 04-745). Final PCR was performed using NEBNext High-Fidelity PCR MM and Nextera general Primer Ad1 and specific Nextera Primer Ad2.n. PCR product was run on a TBE gel (Invitrogen) and libraries were size selected from 250bp to 700bp and cleaned up using 150 ul gel diffusion buffer (500 mM ammonium acetate, pH 8.0, 0.1% SDS, 1 mM EDTA, 10 mM magnesium acetate) and purified using ChIP DNA Clean & Concentrator (Zymo Research). Samples were quantified by Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific) and 75bp paired-end sequenced on a NextSeq 500 (Illumina).