E proteins are required to activate germline transcription of the TCR Vβ8.2 gene

Each TCR V beta gene is regulated by an individual V beta promoter, which becomes active prior to V(D) J recombination and drives germline transcription. it has been shown that V beta gene locus activation and recombination are dependent on the V beta promoter. However, transcription factors that regulate V beta germline transcription remain largely undefined. A major challenge in studying V beta gene germline transcription is the quantitative assessment of relatively low-level transcripts in T-cell progenitors. Here we used the established V beta 8.2(CD2) knock-in mouse model to assess functions of E-protein transcription factors in V beta 8.2 germline transcription. We show that E proteins are required for the activation but not the maintenance of the V beta 8.2 germline transcription during thymocyte development. The activation of V beta 8.2 germline transcription depends more on the E proteins encoded by the E2A gene than by the HEB gene. We further show that IL-7 receptor (IL-7R)-mediated signals are essential for V beta 8.2 germline transcription. We provide evidence that IL-7R expression is only partially controlled by E2A, suggesting a role for E2A in driving V beta 8.2 germline transcription independent of IL-7R activation.