Total RNA was extracted using TRI reagent (Sigma T9424), followed by DNase treatment using the TURBO-DNA-free kit (Life Technologies AM1907). For ChIP-seq, cells (1-2x108) were fixed in 2 mM DSG (Sigma 80424) for 45min and 1% formaldehyde in TS base media for 12 min, both at room temperature (RT). Fixation was stopped by 0.125M glycine. Cells were washed in buffer 1 (10 mM Hepes pH 7. 5, 10 mM EDTA, 0.5 mM EGTA, 0.75% Triton X-100), buffer 2 (10 mM Hepes pH 7.5, 200 mM NaCl, 1 mM EDTA, 0.5 mM EGTA) and lysed in the lysis/sonication buffer (150 mM NaCl, 25 mM Tris pH 7.5, 5 mM EDTA, 0.1% Triton, 1% SDS, 0.5% sodium deoxycholate on ice for 30min. Chromatin was sonicated 30sec on/30off for 25-30 cycles using the BioRuptor (Diagenode), diluted 1/10 with the dilution buffer (150 mM NaCl, 25 mM Tris pH 7.5, 5 mM EDTA, 1% Triton-X 100, 0.1% SDS, 0.5% sodium deoxycholate) and pre-cleared with protein G magnetic Dynabeads (Invitrogen 10004D) pre-blocked with BSA and tRNA. Immunoprecipitation was performed with 350 μg chromatin and 10 μg of antibody over night at 4oC and pre- blocked magnetic beads were added next morning for 7-8h. Beads were washed three times each with buffer A (150 mM NaCl, 25 mM Tris pH 7.5, 5 mM EDTA, 1% Triton-X 100, 0.1% SDS, 0.5% Sodium Deoxycolate), buffer B (50 mM Tris pH8.0, 500 mM NaCl, 0.1% SDS, 0.5% sodium deoxycholate, 1% NP40, 1 mM EDTA), buffer C (50 mM Tris pH8.0, 250 mM LiCl, 0.5% sodium deoxycholate, 1% NP40, 1 mM EDTA). DNA was eluted (1%SDS, 0.1M NaHCO3), reverse cross-linked overnight at 65oC and purified on PCR purification columns (Qiagen). For BS-seq, DNA from vector control (WT) and Tet1 KO cells was bisulfite-converted using the EpiTect kit (Qiagen). The Cdh1 locus was amplified with KAPA HiFi Hotstart Uracil+ ReadyMix (Roche Diagnostics Ltd KK2801). To generate RNA libraries, mRNA was isolated using the Dynabeads mRNA purification kit (Life Technologies 61006) and processed into indexed, strand-specific libraries using the ScriptSeq v2 RNA-Seq Library Preparation Kit (Epicentre SSV21106). Libraries were quantified and assessed using the KAPA Library Quantification Kit (KAPA Biosystems KK4824) and Bioanalyzer 2100 system (Agilent). Indexed libraries were sequenced with a 100bp single-end protocol on an Illumina HiSeq2500 sequencer. ChIP sequencing libraries were quantified as above by Bioanalyzer 2100 system (Agilent) and using the KAPA Library Quantification Kit (KAPA Biosystems KK4824). Indexed libraries from ChIP and Input samples were sequenced with a 50bp paired-end protocol on an Illumina HiSeq2500 sequencer. For BS-seq, libraries were amplified and indexed using KAPA HiFi HotStart ReadyMix (Roche Diagnostic Ltd KK2602). Libraries were quantified as above by Bioanalyzer 2100 system (Agilent) and using the KAPA Library Quantification Kit (KAPA Biosystems KK4824, and sequenced with a 150bp paired-end protocol on a MiSeq sequencer (Illumina), with 10% PhIX spike-in.