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

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  • A Corrigendum to this article was published on 19 March 2013

Abstract

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-deficient mice had aberrant development of effector-memory cells, higher expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl-6 and, unexpectedly, T cell–B cell conjugates and B cell follicles. Collectively, our data show how E2A acted globally to orchestrate development into the T lineage and that Id3 antagonized E2A activity beyond the pre-TCR checkpoint to enforce the naive fate of T cells.

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Figure 1: Analysis of Id3 expression in thymocytes and peripheral T cells from an Id3-GFP reporter mouse strain.
Figure 2: Global occupancy by E2A decreases during β-selection.
Figure 3: Id3 acts to maintain the naive fate of T cells.
Figure 4: Aberrant development of TFH-like cells in the Id3−/− thymus.
Figure 5: Id3 acts to enforce the naive fate of T cells by suppressing intrinsic E2A activity.
Figure 6: Effector-memory–like CD4+ T cells in the Id3−/− thymus.
Figure 7: Abnormal effector-memory and TFH-like compartments in Id3−/− spleen.

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Gene Expression Omnibus

Change history

  • 25 June 2012

    In the version of this article initially published, the GEO accession code for the ChIP–Seq data set was not included. The code is GSE30518. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank A. Goldrath and members of the Murre laboratory for critical reading of the manuscript; G. Hardiman, M. Harabaglia, J. Sprague and C. Ludka for help with Solexa DNA sequencing; N. Varki and the University of California, San Diego Histology Core for histology; and Y. Zhuang (Duke University) for E2a/GFP and E2af/f mice. Supported by the American Recovery and Investment Act (27775A to Y.C.L.) and the US National Institutes of Health (C.M.).

Author information

M.M. designed and did experiments, analyzed data and wrote portions of the manuscript; R.R.R. generated Id3-GFP mice; K.M. did ChIP analyses; Y.C.L. contributed to the analysis of data from ChIP followed by deep sequencing; Y.A. provided advice on ChIP experiments with small number of cells; and C.M. designed experiments, analyzed data and wrote the manuscript.

Correspondence to Cornelis Murre.

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