Transcriptional programs that control expression of the autoimmune regulator gene Aire

Herzig Y, Nevo S, Bornstein C, Brezis MR, Ben-Hur S, Shkedy A, Eisenberg-Bord M, Levi B, Delacher M, Goldfarb Y, David E, Weinberger L, Viukov S, Ben-Dor S, Giraud M, Hanna JH, Breiling A, Lyko F, Amit I, Feuerer M, Abramson J (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nature Immunology Nature Research

Book Volume: 18

Pages Range: 161-172

Journal Issue: 2

DOI: 10.1038/ni.3638

Abstract

Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-Acting and trans-Acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire. In mTECs, however, Aire expression was facilitated by concurrent eviction of CTCF, specific demethylation of exon 2 and the proximal promoter, and the coordinated action of several transcription activators, including Irf4, Irf8, Tbx21, Tcf7 and Ctcfl, which acted on mTEC-specific accessible regions in the Aire locus.

Involved external institutions

Weizmann Institute of Science IL Israel (IL) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Institut Cochin FR France (FR)

How to cite

APA:

Herzig, Y., Nevo, S., Bornstein, C., Brezis, M.R., Ben-Hur, S., Shkedy, A.,... Abramson, J. (2017). Transcriptional programs that control expression of the autoimmune regulator gene Aire. Nature Immunology, 18(2), 161-172. https://doi.org/10.1038/ni.3638

MLA:

Herzig, Yonatan, et al. "Transcriptional programs that control expression of the autoimmune regulator gene Aire." Nature Immunology 18.2 (2017): 161-172.

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