Mutations in the transcriptional regulator, Aire, cause APECED, a polyglandular 
autoimmune disease with monogenic transmission. Animal models of APECED have 
revealed that Aire plays an important role in T cell tolerance induction in the 
thymus, mainly by promoting ectopic expression of a large repertoire of 
transcripts encoding proteins normally restricted to differentiated organs 
residing in the periphery. The absence of Aire results in impaired clonal 
deletion of self-reactive thymocytes, which escape into the periphery and attack 
a variety of organs. In addition, Aire is a proapoptotic factor, expressed at 
the final maturation stage of thymic medullary epithelial cells, a function that 
may promote cross-presentation of the antigens encoded by Aire-induced 
transcripts in these cells. Transcriptional regulation by Aire is unusual in 
being very broad, context-dependent, probabilistic, and noisy. 
Structure/function analyses and identification of its interaction partners 
suggest that Aire may impact transcription at several levels, including 
nucleosome displacement during elongation and transcript splicing or other 
aspects of maturation.