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E-proteins directly regulate expression of activation-induced deaminase in mature B cells

Nature Immunology volume 4, pages 586–593 (2003)Cite this article

Abstract

Activated mature B cells in which the DNA-binding activity of E-proteins has been disrupted fail to undergo class switch recombination. Here we show that activated B cells overexpressing the antagonist helix-loop-helix protein Id3 do not induce expression of the murine Aicda gene encoding activation-induced deaminase (AID). A highly conserved intronic regulatory element in Aicda binds E-proteins both in vitro and in vivo. The transcriptional activity of this element is regulated by E-proteins. We show that the enforced expression of AID in cells overexpressing Id3 partially restores class switch recombination. Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription.

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Figure 1: Aicda expression in activated B cells overexpressing the inhibitory HLH protein Id3.
Figure 2: Activation of Aicda transcription by E47.
Figure 3: An intronic regulatory region in the Aicda locus is activated by E-proteins.
Figure 4: E47 and E2-2 bind to E-box sites in the AIDE1 enhancer in activated B cells.
Figure 5: In vivo occupancy of the E-box sites in the AIDE1 enhancer in activated B cells.
Figure 6: Ectopic expression of AID in Id3-expressing B cells partially rescues CSR.
Figure 7: Germline transcription of the Ig S region in B cells expressing Id3.

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Acknowledgements

We thank K. Choi for the E47R vector, and I. Engel and R. Rivera for comments on the manuscript. C.E.S. was supported by a postdoctoral fellowship from the Canadian Institute of Health Research. Y.A. was supported by a fellowship from Japan Science and Technology. This work was supported by grants from the National Institutes of Health to C.M.

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  1. Camil Elie Sayegh and Melanie W Quong: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biological Sciences, University of California San Diego, La Jolla, 92093, California, USA

    Camil Elie Sayegh, Melanie W Quong, Yasutoshi Agata & Cornelis Murre

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Correspondence to Cornelis Murre.

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Sayegh, C., Quong, M., Agata, Y. et al. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat Immunol 4, 586–593 (2003). https://doi.org/10.1038/ni923

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