Journal
NATURE IMMUNOLOGY
Volume 16, Issue 9, Pages 942-949Publisher
NATURE PORTFOLIO
DOI: 10.1038/ni.3247
Keywords
-
Categories
Funding
- US National Institutes of Health [DK060027]
- US National Institutes of Health (Children's Hospital in Pediatric Gastroenterology)
- Boehringer Ingelheim Fonds
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available