AI Article Synopsis
- Aire is a transcriptional regulator that promotes the expression of many tissue-restricted antigens in medullary thymic epithelial cells (mTECs).
- The regulation of Aire's own expression involves complex interactions, including the insulation of its gene locus by CTCF, which is disrupted in mTECs to allow for Aire expression.
- Key transcription activators like Irf4, Irf8, Tbx21, Tcf7, and Ctcfl play significant roles in facilitating the demethylation and activation of the Aire gene in specific regions of mTECs.
Article 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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| http://dx.doi.org/10.1038/ni.3638 | DOI Listing |
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