FOXP3 actively represses transcription by recruiting the HAT/HDAC complex.
The Forkhead box protein P3 (FOXP3) is a master cell lineage modulator in CD4(+)CD25(+) natural regulatory T cell (Treg) development. The Treg set of cells, also called T suppressor cells, play an essential role in natural Treg-mediated suppression of various types of immune cells. Suppression can be manifest by a cell-cell contact set of events, and recent evidence also supports soluble mediators. FOXP3 was previous identified as a passive transcriptional repressor which associates with nuclear factor of activated T-cells, cytoplasmic, and calcineurin-dependent 2 (NFATc2) as well as several other transcriptional factors including nuclear factor kappa-B (NFkappaB) and acute myeloid leukemia 1(AML1)/runt-related transcription factor 1(RUNX1). We found FOXP3 could actively repress transcription by recruiting distinct histone acetyltransferases and histone deacetylases to function as a co-repressor complex. The identification of enzymatic factors operative as essential participants in FOXP3-mediated transcriptional repression provides a practical basis for therapeutically modulating the activity of FOXP3 in immune suppression. Here we briefly summarize recent progress in our understanding of the biochemistry of FOXP3-mediated transcriptional regulation.
Li
Bin
B
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Greene
Mark I
MI
D042002:Chromatin Assembly and Disassembly / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D046912:Multiprotein Complexes; D014157:Transcription Factors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases