The complex of CBFB and RUNX1 (AML1) controls transcription of the FOXP3 gene. FOXP3 is a transcription factor that acts as a key regulator of development and function of regulatory T lymphocytes (Tregs). Tregs are CD25+CD4+ T lymphocytes involved in suppression of aberrant immune responses seen in autoimmune diseases and allergies. FOXP3 can bind to RUNX1 and control transcriptional activity of the RUNX1:CBFB complex. RUNX1 stimulates transcription of IL2 and IFNG1 (IFN-gamma), and the expression of these two genes is repressed upon binding of FOXP3 to RUNX1. The complex of FOXP3 and RUNX1, on the other hand, stimulates transcription of cell surface markers of Tregs, such as CD25, CTLA-4 and GITR. In the absence of FOXP3, RUNX1 represses transcription of these genes (Shevach 2000, Maloy and Powrie 2001, Sakaguchi 2004, Ono et al. 2007, Kitoh et al. 2009).
The RUNX1:CBFB complex directly stimulates transcription of the CR1 gene, encoding Complement receptor type 1 (CD35) (Kim et al. 1999, Rho et al. 2002). Expression of CR1 on the surface of activated T cells contributes to generation of Tregs (Torok et al. 2015).