Chromatin lysates were prepared as follows: Pooled organoids from 12 wells (approx. 5 mill cells) were mechanically disrupted in PBS and centrifugated to remove the matrigel. Followed by fixation in 1% Formaldehyde in PBS, rotating at room temperature for 15 minutes, and quenched with Glycine at 250 mM final concentration. The following steps, including ChIP, were performed as previously described (Ramos-Pittol et al. 2018). Sequencing libraries were prepared using the Rapid DNA-Seq Kit (NEXTflex)