Nuclei isolation protocol: The crypts were resuspended in 2 ml TrypLE Express with 10 μM Y-27632 and 0.5 mM N-acetylcysteine, pipetted carefully through a 1 ml pipet for dissociation at room temperature. The suspension was then topped up with 20 ml 10% fetal bovine serum (FBS) in PBS and the cells were filtered through a 40 μm cell strainer. The cell suspension was then pelleted at 465 x g, 4 °C for 5 min. The cells were then resuspended in 5 ml ice cold HBSS and re-pelleted and this step was repeated to remove the TrypLE and FBS. The cells were the re-supended in 2 ml 1 % containing N-buffer (15 mM HEPES, pH 7.5, 10% sucrose, 60 mM KCl, 15 mM NaCl, 0.5 mM EGTA, 0.2 mM PMSF, 1 x CompleteTM [Roche] protease inhibitor, 50 mM sodiumbutyrate) and incubated 15 min on ice. This mix was then overlayed on a 5 ml sucrose cushion (30% sucrose in N-buffer) and nuclei were pelleted for 15 min at 1300 x g, 4 °C. Nuclei were taken up in 100 μl ice cold nuclei storage (25 mM Tris-HCl, pH 7.5, 100 mM potassium acetate, 10 mM MgCl2, 2 mM Spermidine) and counted. ATAC-seq Libraries were generated from 50 000 cells as described by Buenostro using the Nextera kit from Illumina and TruSeq primers. Libraries were sequenced on an Illumina HiSeq as 50 bp Paired End reads.