Project description:Autoimmune regulator (Aire) is a unique transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for induction of immunological self-tolerance. Although several recent studies provided very important molecular insights into how Aire operates, a more comprehensive understanding of this process still remains elusive. Here we demonstrate that a lysine deacetylase Sirtuin-1 (Sirt1) is predominantly expressed in mature Aire+ mTECs, where it is required for expression of Aire-dependent TRA genes and a subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and uncovers a unique functional role for Sirt1 in preventing organ-specific autoimmunity. ~100ng of total RNA isolated by Trizol extraction from MHC-II low and high mTECs (pool of 3 mice) was used to generate poly-A-selected transcriptome libraries using the non-directionnal TruSeq V3 RNA Sample Prep Kit (without additional pre-amplification) following the manufacturer's protocols. Enrichment of DNA fragment with adapter molecules on both ends was done using 15 cycles of PCR amplification using the Illumina PCR mix and primer cocktail. Paired-end (2 × 100 bp) sequencing was performed using the Illumina HiSeq2000 machine.

2015-05-25 | E-GEOD-68190 | biostudies-arrayexpress

Histone H3K4me1 strongly activates the DNase I hypersensitive sites in super-enhancers than those in typical enhancers.

Project description: Not available

| S-EPMC8264496 | biostudies-literature

Sirt1 is essential for Aire-mediated induction of central immunological tolerance

2015-05-25 | GSE68190 | GEO

Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity.

Project description: Not available

| S-EPMC2572939 | biostudies-literature

Deletional tolerance mediated by extrathymic Aire-expressing cells.

Project description: Not available

| S-EPMC2532844 | biostudies-literature