Pluto Bioinformatics

GSE121279: RNA-seq and ChIP-seq to study how transcription factor Foxp1 regulates Foxp3 binding to chromatin and coordinates regulatory T cell function

Bulk RNA sequencing

Regulatory T (Treg) cells, whose differentiation and function are controlled by transcription factor Foxp3, express high amounts of a closely related family member Foxp1, which is also expressed in quiescent naive T cells. Here we explored Foxp1 function in Treg cells. We found that a large number of Foxp3-bound genomic sites in Treg cells were occupied by Foxp1 in both Treg and conventional T cells. In Treg cells, Foxp1 markedly increased Foxp3 binding to these sites, which were enriched for canonic forkhead and Ets binding motifs. Foxp1 deficiency in Treg cells resulted in their impaired function and competitive fitness associated with markedly reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 and increased SATB1 expression. The characteristic patterns of CD25, Foxp3, and CTLA-4 expression in Treg cells were rescued, at least in part, upon strong IL-2 signaling. Our studies suggest that in addition to the Foxp1-mediated regulation of quiescence that is common to Treg and conventional T cells, Foxp1 has an essential non-redundant function in Treg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells. SOURCE: Yuri Pritykin Memorial Sloan Kettering Cancer Center