GSE30518
Opposing roles of E2A and Id3 that orchestrate and enforce the naive T cell fate
It is established that E2A and its antagonist, Id3, modulate developmental progression at the pre-TCR and TCR checkpoints.  Here we show at a global scale how E2A promotes commitment to the T cell lineage and how pre-TCR mediated signalling affects E2A genome-wide occupancy.  We find aberrant development of CD4 memory-like and TFH-like cells, T-B cell conjugates and, remarkably, B cell follicles in Id3-/-thymi.  We also find that Id3-/-CD4 splenocytes exhibit increased numbers of TFH-like cells.  We propose a model in which Id3 modulates the naive versus effector/memory cell fate.  Collectively, these data show how E2A acts globally to orchestrate T-lineage development and that Id3 antagonizes E2A activity beyond the pre-TCR checkpoint to enforce the naive T cell fate. Overall design: ChIP-Seq was performed in thymocytes isolated from either untreated Rag2-/-mice (DN3 cells) or Rag2-/- mice injected with anti-CD3e antibody (DN4 cells). ChIP used antibodies against either E2A or H3K4me1.