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000119335 0247_ $$2doi$$a10.1038/ni.3638
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000119335 0247_ $$2ISSN$$a1529-2916
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000119335 041__ $$aeng
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000119335 1001_ $$aHerzig, Yonatan$$b0
000119335 245__ $$aTranscriptional programs that control expression of the autoimmune regulator gene Aire.100
000119335 260__ $$aNew York, NY$$bNature America Inc.$$c2017
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000119335 520__ $$aAire 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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000119335 7001_ $$aNevo, Shir$$b1
000119335 7001_ $$aBornstein, Chamutal$$b2
000119335 7001_ $$aBrezis, Miriam R$$b3
000119335 7001_ $$aBen-Hur, Sharon$$b4
000119335 7001_ $$aShkedy, Aya$$b5
000119335 7001_ $$aEisenberg-Bord, Michal$$b6
000119335 7001_ $$aLevi, Ben$$b7
000119335 7001_ $$0P:(DE-He78)a4340add02b610f9dbdba2dc909cbd09$$aDelacher, Michael$$b8
000119335 7001_ $$aGoldfarb, Yael$$b9
000119335 7001_ $$aDavid, Eyal$$b10
000119335 7001_ $$aWeinberger, Leehee$$b11
000119335 7001_ $$aViukov, Sergey$$b12
000119335 7001_ $$0http://orcid.org/0000-0001-9604-1939$$aBen-Dor, Shifra$$b13
000119335 7001_ $$aGiraud, Matthieu$$b14
000119335 7001_ $$0http://orcid.org/0000-0003-2042-9974$$aHanna, Jacob H$$b15
000119335 7001_ $$0P:(DE-He78)75fed3121e92379462cce5d2267320b7$$aBreiling, Achim$$b16$$udkfz
000119335 7001_ $$0P:(DE-He78)a8d53a8cdc716390a6cbacdead227143$$aLyko, Frank$$b17
000119335 7001_ $$aAmit, Ido$$b18
000119335 7001_ $$0P:(DE-He78)f0638edf1d3f61c0d7ebb587f511733f$$aFeuerer, Markus$$b19
000119335 7001_ $$aAbramson, Jakub$$b20
000119335 773__ $$0PERI:(DE-600)2026412-4$$a10.1038/ni.3638$$gVol. 18, no. 2, p. 161 - 172$$n2$$p161 - 172$$tNature immunology$$v18$$x1529-2916$$y2017
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