Journal Article

DKFZ-2017-00090

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transcriptional programs that control expression of the autoimmune regulator gene Aire.100

Herzig, Y. ; Nevo, S. ; Bornstein, C. ; Brezis, M. R. ; Ben-Hur, S. ; Shkedy, A. ; Eisenberg-Bord, M. ; Levi, B. ; Delacher, M.DKFZ* ; Goldfarb, Y. ; David, E. ; Weinberger, L. ; Viukov, S. ; Ben-Dor, S. ; Giraud, M. ; Hanna, J. H. ; Breiling, A.DKFZ* ; Lyko, F.DKFZ* ; Amit, I. ; Feuerer, M.DKFZ* ; Abramson, J.

2017
Nature America Inc. New York, NY

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Please use a persistent id in citations: 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.

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Contributing Institute(s):

1. Epigenetik (A130)
2. Immuntoleranz (D100)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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