Deciphering the TET3 interactome in primary thymic developing T cells

Ten-eleven translocation (TET) proteins are DNA dioxygenases that mediate active DNA demethylation. TET3 is the most highly expressed TET protein in thymic developing T cells. TET3, either independently or in cooperation with TET1 or TET2, has been implicated in T cell lineage specification by regulating DNA demethylation. However, TET-deficient mice exhibit complex phenotypes, suggesting that TET3 exerts multifaceted roles, potentially by interacting with other proteins. We performed liquid chromatography with tandem mass spectrometry in primary developing T cells to identify TET3 interacting partners in endogenous, in vivo conditions. We discover TET3 interacting partners. Our data establish that TET3 participates in a plethora of fundamental biological processes, such as transcriptional regulation, RNA polymerase elongation, splicing, DNA repair, and DNA replication. This resource brings in the spotlight emerging functions of TET3 and sets the stage for systematic studies to dissect the precise mechanistic contributions of TET3 in shaping T cell biology. [Display omitted] •We identify TET3 interacting partners in developing thymocytes•TET3 participates in complexes to regulate polymerase elongation and splicing•TET3 interacts with proteins involved in DNA repair and replication•TET3 participates in networks orchestrated by CTCF, BCL11b, and GATA3 Biochemistry; Molecular biology; Molecular interaction; Proteomics