The DNA demethylase TET1 recognises chromatin via nucleosome engagement of its N-terminal region

TET1 is a DNA demethylase critical for mammalian embryonic development, yet how it is recruited to its chromatin substrate remains poorly understood. Here we identify a previously uncharacterized N-terminal region of TET1 that directly binds nucleosomes and promotes chromatin binding in mouse embryonic stem cells. Robust chromatin association was evidenced by fluorescence recovery after photobleaching during interphase and chromosome retention throughout mitosis. A 2.47 angstroms cryo-EM structure of the TET1-nucleosome complex reveals recognition of the nucleosome acidic patch through a canonical arginine anchor centred on R75, with additional contacts extending along the H2B surface. Biochemical and cellular analyses validate this interaction and demonstrate its contribution to TET1 chromatin engagement. The region is absent from TET2 and TET3 and displays strong conservation within mammals, indicating that direct nucleosome recognition is a specialized feature of TET1. Together, these findings uncover a previously unknown chromatin-binding module in TET1 and establish a structural basis for its interaction with nucleosomes.