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FOXP3 Actively Represses Transcription by Recruiting the HAT/HDAC Complex

Bin Li and Mark I. Greene

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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 (NF-κB) 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 corepressor 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.

Authors

Bin Li

The University of Pennsylvania; Philadelphia, Pennsylvania

Mark I. Greene

The University of Pennsylvania; Philadelphia, Pennsylvania

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.