Table 1.
AIRE partners during the promiscuous gene expression in medullary thymic epithelial cells23, 43, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109
| Protein symbol | Name | Function | AIRE domain involved |
|---|---|---|---|
| Proteins that interact concomitantly with AIRE protein | |||
| RNA Pol II | RNA Polymerase II | Starts the gene transcription after Aire‐partners‐mediated activation and phosphorylation | PHD‐2 |
| H3K4 | Unmethylated histone H3 lysine 4 | Recruits AIRE protein at the transcription start site(s) (TSS) | PHD‐1 |
| ATF7IP–MBD1 | Activating transcription factor 7‐interacting protein–methyl‐CpG‐binding domain protein 1 | Mediates AIRE protein recruitment by methylation of CpG island in repressed genes | SAND |
| DNA‐PK | DNA‐dependent protein kinase | Phosphorylates the AIRE protein, indicates where Aire starts the gene transcription by phosphorylation of H2AX histone that recognize DNA breaks | PHD‐2 |
| P‐TEFb | Positive transcription elongation factor b | Promotes that AIRE protein unleashes stalled RNA Pol II | C‐Terminus |
| HNRNPL | Heterogeneous nuclear ribonucleoprotein L | Participates in the RNA elongation mediated by pTEFb | C‐Terminus |
| BRD4 | Bromodomain‐containing 4 | Binds directly to AIRE protein and forms a complex with pTEFb and HNRNPL to induce the unleashes of stalled RNA Pol II | CARD |
| EFTUD2 | Elongation factor TU GTP‐binding domain‐containing protein 2 | Involved in the alternative splicing of RNA mediated by AIRE protein | ND |
| SNRPB | Small nuclear ribonucleoprotein‐associated proteins B | ||
| SRSF1 | Serine/arginine‐rich splicing factor 1 | ||
| SIRT1 | Deacetylase sirtuin 1 | Deacetylates lysine residues of AIRE protein leading to its activation | Lysine residues NLS (121–261) |
| HDAC1‐2 | Histone deacetylase 1 and 2 | Exports and stabilizes AIRE protein in the nucleus | |
| CBP, p300 | CREB‐binding protein | Acetylates the lysine residues of AIRE protein leading to repression of its activity | |
| HIPK2 | Homeodomain‐interacting protein kinase 2 | Phosphorylates AIRE protein suppressing its activation | PHD‐2 |
| FBXO3 | F‐box protein 3 E3 ubiquitin ligase | Ubiquitinates AIRE protein promoting and increasing its affinity to pTEFb factor | N terminus (207) |
| MARCH 8 | Membrane‐bound E3 ubiquitin ligases | Regulates the MHC‐II expression in AIRE+ medullary thymic epithelial cell (mTECs) | ND |
| PIAS1 | Protein inhibitor of activated STAT | Possible sumoylation of AIRE protein regulating its activation | CARD |
| Importins | Importins α1, α3 and α5 | Exporting of AIRE protein to the nucleus | NLS |
| TOP2A | DNA topoisomerase IIα | Assiciates with AIRE protein and promotes DNA breaks at TSS | PHD‐2 |
| Proteins that directly interact with the Aire gene (at DNA level) | |||
| ERα | Oestrogen receptor α | Induces methylation of the promoter region of Aire gene leading to decreasing of Aire expression | Promoter |
| AR | Androgen receptor | The accumulation of AR in the promoter region of Aire gene leads to its activation | Promoter |
| JMJD6 | Histone arginine demethylase | Promotes the splicing of intron 2 of Aire mRNA | Intron 2 |
| CNS1 | Conserved non‐coding sequence 1 | Conserved region of 90 nucleotides that regulate the Aire gene activation through RANK and nuclear factor‐κB signalling | Between Aire and Dnmt3l genes |
| IRF4, IRF8, TBX21 and TCF7 | Interferon regulatory factor 1 e 8, T‐box transcription factor, transcription factor 7 | Form a transcriptional complex necessary for the Aire gene expression in mTECs | Promoter |
| CTCF | CCCTC‐binding factor | Represses the Aire gene expression inhibiting the interaction of IRF4, IRF8, TBX21 and TCF7 complex with the Aire promoter | TSS and 3′ UTR |