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. 2020 Mar 9;160(1):24–37. doi: 10.1111/imm.13178

Figure 2.

Figure 2

A model for Runx1‐guided control of Treg‐type transcriptome. AML1/Runx1 has different roles in Foxp3− T‐cells (conventional T‐cells) (a, b) and Foxp3+ Treg (c, d). (a) When T‐cells are matured, the AML1/Runx1‐CBF‐β complex may bind primed and poised enhancers, which are transcriptionally inactive, and AML1/Runx1 is poised to execute its function for T‐cell differentiation and response. Primed enhancers are marked by H3K4me1 but not by H3K27me3. Poised enhancers are similar to active enhancers in p300 binding and nucleosome depletion, but are marked by H3K27me3 in addition to H3K4me1. Histones at the promoter are marked by H3K4me3, which is the feature of active promoter. In poised enhancer, AML1/Runx1 presumably interacts with p300, while PRC2 and HDACs actively suppress p300‐mediated histone acetylation and prevent transcriptional activation. (b) Upon cognate antigen recognition, TCR signals activate its downstream transcription factors, including NF‐κB, NFAT and AP‐1, which are recruited to promoters and enhancers of AML1/Runx1‐bound genes. This will form a p300‐containing enhanceosome, which acetylates histones together with other HATs such as Kat2b and TIP60, increasing H3K27Ac, and enhances RNA polymerase II (Pol II)‐mediated transcription at the transcription start site (TSS). (c) In Treg, Foxp3 is highly expressed and TCR signals are regularly conveyed. When Foxp3 expression is induced, whether in the thymus or in the periphery, T‐cells have received strong TCR signals. Some genes such as Il2 have repressed enhancers, to which the Foxp3‐AML1/Runx1 complex binds. Foxp3 and AML1/Runx1 may further recruit transcriptional corepressors such as NCoR1/NCoR2 (through HDAC3) and TLE, respectively (Fig. 1). (d) Treg highly express activation‐induced proteins including CD25 and coinhibitory molecules, which transcriptional activities are sustained with the help of Foxp3 and infrequent‐but‐regular TCR signals. Foxp3 is considered to stabilize TCR signal‐induced enhanceosomes by interacting with AML1/Runx1 and TCR signal downstream transcription factors.