TY  - JOUR
AU  - Herzig, Yonatan
AU  - Nevo, Shir
AU  - Bornstein, Chamutal
AU  - Brezis, Miriam R
AU  - Ben-Hur, Sharon
AU  - Shkedy, Aya
AU  - Eisenberg-Bord, Michal
AU  - Levi, Ben
AU  - Delacher, Michael
AU  - Goldfarb, Yael
AU  - David, Eyal
AU  - Weinberger, Leehee
AU  - Viukov, Sergey
AU  - Ben-Dor, Shifra
AU  - Giraud, Matthieu
AU  - Hanna, Jacob H
AU  - Breiling, Achim
AU  - Lyko, Frank
AU  - Amit, Ido
AU  - Feuerer, Markus
AU  - Abramson, Jakub
TI  - Transcriptional programs that control expression of the autoimmune regulator gene Aire.100
JO  - Nature immunology
VL  - 18
IS  - 2
SN  - 1529-2916
CY  - New York, NY
PB  - Nature America Inc.
M1  - DKFZ-2017-00090
SP  - 161 - 172
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:27941786
DO  - DOI:10.1038/ni.3638
UR  - https://inrepo02.dkfz.de/record/119335
ER  -