Cells were washed twice in ice-cold PBS and pelleted by centrifugation. The cells were resuspended in 10 ml ice-cold PBS and freshly prepared 0.25M disuccinimidyl glutarate (DSG) stock solution (dissolved in DMSO) to obtain a final concentration of 2mM DSG in PBS (ThermoFisher Scientific, Cat: 20593) and incubated at a rotating wheel for 30 min to allow equilibration to room temperature. Then, formaldehyde (Sigma, Cat: 252549) was added to obtain a final concentration of 1% and rotated for another 10 min at room temperature. Finally, the crosslinking reaction was stopped by addition of glycine to a final concentration of 125mM. The cells were spun down for 5 min at 350 x g rpm at room temperature and washed twice with ice-cold PBS. The cells were then resuspended in 5 mL SDS Buffer (50mM Tris-HCl pH 8.1, 100mM NaCl, 5mM EDTA, 0.5% SDS) containing 1 mM Phenylmethylsulfonyl fluoride (PMSF) and allowed to rotate for another 5 min. Finally, the cells were pelleted and resuspended in IP buffer (100mM Tris-HCl pH 8.6, 100mM NaCl, 5mM EDTA, 0.3% SDS, 1.7% TritonX-100) with proteinase inhibitors according to pellet size. Chromatin dissolved in IP buffer was sheared to an average size of 200-500 bp DNA fragments in a Bioruptor (Diagenode). The sonicated chromatin was diluted in SDS-free IP buffer to achieve a concentration of 0.1% SDS, spun down at 20,000 x g for 20 min to remove insoluble chromatin fraction and precleared with protein G Sepharose beads (GE healthcare) prior to immunoprecipitation. For immunoprecipitation of endogenous TET2, 1µg affinity-purified rabbit polyclonal antibody raised against N-terminal TET2 protein (TET2-N) (Helin lab) was incubated with 300µg chromatin overnight. The chromatin-antibody complexes were captured in a 3h incubation with protein-G Sepharose beads (GE healthcare). Washes of chromatin-antibody-bead complexes were performed as follows: Three washes with ice-cold 150mM wash buffer (20mM Tris-HCl pH 8.0, 150mM NaCl, 2mM EDTA, 0.1% SDS, 1% Triton X-100), two washes with ice-cold 500mM wash buffer (20mM Tris-HCl pH 8.0, 500mM NaCl, 2mM EDTA, 0.1% SDS, 1% Triton X-100), and one wash with ice-cold IP buffer with a final concentration of 0.1% SDS. After the last wash, DNA from TET2-N immunoprecipitations was decrosslinked by overnight incubation at 65oC in decrosslinking solution (1% SDS, 0.1M NaHCO3). IP'ed DNA was purified using the QIAquick PCR purification kit (Qiagen) according to manufacturer's instructions. ChIP-seq libraries for Illumina sequencing was prepared using the NEBNext Ultra II DNA library preparation kit (New England Biolabs) using an input of 1-3ng of IP'ed DNA (quantified using DNA HS assay kit (Qubit)) following the manufacturer's instructions. Adaptor-ligated fragments were size-selected using AMPure XP beads (Beckman Coulter) to retain inserts of approximately 200bp prior to PCR amplification. Equimolar amounts of sample, with compatible indexes, were pooled and sequenced on Illumina NextSeq 550 (75bp single-end).