The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance
Copyright policy )The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance
The maintenance of immune tolerance requires the deletion of self-reactive T cells in the thymus. The expression of tissue-specific antigen genes (TSAs) by thymic epithelial cells is critical for this process and depends on the activity of the Autoimmune Regulator (Aire) protein, however, the molecular mechanism(s) Aire uses to target TSA gene loci are unknown. Here we identified two Aire-interacting proteins – activating transcription factor 7 interacting protein (ATF7ip) and methyl CpG binding protein 1 (MBD1) –that are required for Aire’s targeting of TSA geneloci. Moreover, Mbd1−/− mice developed pathological autoimmunity and had a defect in Aire-dependent thymic TSA gene expression underscoring the critical importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.
- University of North Carolina at Chapel Hill United States
- University of California, San Francisco United States
- Kings College London, University of London United Kingdom
- King's College London United Kingdom
Knockout, Immunoblotting, Inbred C57BL, Transfection, Autoantigens, Mice, Two-Hybrid System Techniques, 616, Immune Tolerance, Animals, Humans, Immunoprecipitation, Oligonucleotide Array Sequence Analysis, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Flow Cytometry, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, HEK293 Cells, Gene Expression Regulation, Central Tolerance, Protein Binding, Transcription Factors
Knockout, Immunoblotting, Inbred C57BL, Transfection, Autoantigens, Mice, Two-Hybrid System Techniques, 616, Immune Tolerance, Animals, Humans, Immunoprecipitation, Oligonucleotide Array Sequence Analysis, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Flow Cytometry, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, HEK293 Cells, Gene Expression Regulation, Central Tolerance, Protein Binding, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).79 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!