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Opposing roles of E2A and Id3 that orchestrate and enforce the naive T cell fate


ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus

SUBMITTER: Yin Lin 

PROVIDER: E-GEOD-30518 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.

Miyazaki Masaki M   Rivera Richard R RR   Miyazaki Kazuko K   Lin Yin C YC   Agata Yasutoshi Y   Murre Cornelis C  

Nature immunology 20110821 10


It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a bimodal pattern in the effector-memory population. We show how E2A promoted T lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide occupancy. Thymi in Id3-deficien  ...[more]

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