The villi were isolated from the small intestine while the Lgr5-GFP+ ISCs were sorted from the isolated crypts Villi cells or ISCs were cross-linked with 1% formaldehyde and chromatin sonicated. Chromatin was precipitated with specific antibody, which was further purified using magnetic protein A coupled beads, and recovered DNA was used for high-throughput sequencing. Libraries were prepared according to Illumina's instructions accompanying the DNA Sample Kit (Part# 0801-0303).