Abstract:
:The transcription factor Aire controls immunological tolerance by inducing the ectopic thymic expression of many tissue-specific genes, acting broadly by removing stops on the transcriptional machinery. To better understand Aire's specificity, we performed single-cell RNA-seq and DNA-methylation analysis of Aire-sufficient and Aire-deficient medullary epithelial cells (mTECs). Each of Aire's target genes was induced in only a minority of mTECs, independently of DNA-methylation patterns, as small inter-chromosomal gene clusters activated in concert in a proportion of mTECs. These microclusters differed between individual mice. Thus, our results suggest an organization of the DNA or of the epigenome that results from stochastic determinism but is 'bookmarked' and stable through mTEC divisions, which ensures more effective presentation of self antigens and favors diversity of self-tolerance between individuals.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Meredith M,Zemmour D,Mathis D,Benoist Cdoi
10.1038/ni.3247subject
Has Abstractpub_date
2015-09-01 00:00:00pages
942-9issue
9eissn
1529-2908issn
1529-2916pii
ni.3247journal_volume
16pub_type
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