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Summary Estrogen receptor-α (ER) drives tumor development in ER-positive (ER+) breast cancer. The transcription factor GATA3 has been closely linked to ER function, but its precise role in this setting remains unclear. Quantitative proteomics was used to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, few proteins were lost from the ER complex in the absence of GATA3, with the only major change being depletion of the dioxygenase TET2. TET2 binding constituted a near-total subset of ER binding in multiple breast cancer models, with loss of TET2 associated with reduced activation of proliferative pathways. TET2 knockdown did not appear to change global methylated cytosine (5mC) levels; however, oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) was significantly reduced, and these events occurred at ER enhancers. These findings implicate TET2 in the maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes., Graphical Abstract, Highlights • TET2 is identified as a component of the ER complex through depletion of GATA3 • TET2 global chromatin binding tracks that of ER/GATA3 in multiple breast cancer models • Loss of TET2 is linked to dysregulated expression of ER target genes • Concurrent loss of 5hmC at ER sites provides insights into TET2’s role in ER activity, Broome et al. use quantitative proteomics and chromatin immunoprecipitation to explore the contribution of TET2 to ER/GATA3 transcriptional activity. TET2 tracks ER chromatin binding in breast cancer models and plays an essential role in the maintenance of 5-hydroxymethylcytosine at ER enhancers, revealing a role for TET2 in ER-driven gene expression.