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Updated: May 3, 2026

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
Published on: October 6, 2019
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance
Michael Waterfield1, Imran S Khan2, Jessica T Cortez2
11] Diabetes Center, University of California San Francisco, San Francisco, California, USA. [2] Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
Abstract:
The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechanisms Aire uses to target loci encoding TSAs are unknown. Here we identified two Aire-interacting proteins known to be involved in gene repression, ATF7ip and MBD1, that were required for Aire's targeting of loci encoding TSAs. Moreover, Mbd1(-/-) mice developed pathological autoimmunity and had a defect in Aire-dependent thymic expression of genes encoding TSAs, which underscores the importance of Aire's interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.
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