Aire controls gene expression in the thymic epithelium with ordered stochasticity.

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 Immunol

journal_title

Nature immunology

authors

Meredith M,Zemmour D,Mathis D,Benoist C

doi

10.1038/ni.3247

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

942-9

issue

9

eissn

1529-2908

issn

1529-2916

pii

ni.3247

journal_volume

16

pub_type

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