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Cooperativity between head-to-head dimerization and head-to-tail multimerization of FoxP3 transcription factor

ABSTRACT: FoxP3, an essential transcription factor for regulatory T cells (Tregs), forms higher-order multimers on TnG microsatellites in the genome. Although a previous study has shown that FoxP3 can form head-to-head (H-H) dimers on inverted repeats of forkhead motifs (IR-FKHM), in vivo evidence for this configuration was elusive. An unbiased FoxP3 pull-down sequencing approach identified a wide range of sequences supporting H-H dimerization, enabling systematic genomic analysis. This work revealed that FoxP3 binds DNA in Tregs as both H-H dimers and higher-order multimers, often incorporating one half-site of the H-H dimer into TnG repeats. A robust H-H interaction can seed multimerization on adjacent TnG repeats, enhancing assembly even on suboptimal sequences. Unlike other FoxP transcription factors, H-H dimerization is unique to FoxP3. Chimeric construct analyses identified a loop adjacent to the forkhead domain as the determinant for this distinctive function, underscoring a unique synergism between two binding modes.

ORGANISM(S): Mus musculus

PROVIDER: GSE294472 | GEO | 2025/10/31

REPOSITORIES: GEO

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Cooperativity between head-to-head dimerization and head-to-tail multimerization of FoxP3 transcription factor

Project description:Cooperativity between head-to-head dimerization and head-to-tail multimerization of FoxP3 transcription factor

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