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Proc Natl Acad Sci U S A ; 102(20): 7233-8, 2005 May 17.
Article in English | MEDLINE | ID: mdl-15883360

ABSTRACT

Autoimmune regulator (aire) is a transcription factor that controls the self-reactivity of the T cell repertoire. Although previous results indicate that it exerts this function in part by promoting ectopic expression of a battery of peripheral-tissue antigens in epithelial cells of the thymic medulla, recent data argue for additional roles in negative selection of thymocytes by medullary cells. As one approach to exploring such roles, we performed computational analyses of microarray data on medullary RNA transcripts from aire-deficient versus wild-type mice, focusing on the genomic localization of aire-controlled genes. Our results highlight this molecule's transcriptional activating and silencing roles and reveal a significant degree of clustering of its target genes. On a local scale, aire-regulated clusters appeared punctate, with aire-controlled and aire-independent genes often being interspersed. This pattern suggests that aire's action may not be a simple reflection of the wide action of a chromatin remodeling enzyme. Analysis of the identity of certain of the clustered genes was evocative of aire's potential roles in antigen presentation and the coordination of intrathymic cell migration: for example, major histocompatibility complex class I and class II gene products and certain chemokine genes are targets of aire-regulated transcription.


Subject(s)
Chromosomes, Mammalian/genetics , Gene Expression Regulation/genetics , Thymus Gland/metabolism , Transcription Factors/metabolism , Animals , Cluster Analysis , Computational Biology/methods , Major Histocompatibility Complex/genetics , Mice , Oligonucleotide Array Sequence Analysis , Sensitivity and Specificity , Thymus Gland/cytology , Transcription Factors/genetics , AIRE Protein
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