4wk8
FOXP3 forms a domain-swapped dimer to bridge DNA
Structural highlights
DiseaseFOXP3_HUMAN Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionFOXP3_HUMAN Probable transcription factor. Plays a critical role in the control of immune response. Publication Abstract from PubMedFOXP3 is a lineage-specific transcription factor that is required for regulatory T cell development and function. In this study, we determined the crystal structure of the FOXP3 forkhead domain bound to DNA. The structure reveals that FOXP3 can form a stable domain-swapped dimer to bridge DNA in the absence of cofactors, suggesting that FOXP3 may play a role in long-range gene interactions. To test this hypothesis, we used circular chromosome conformation capture coupled with high throughput sequencing (4C-seq) to analyze FOXP3-dependent genomic contacts around a known FOXP3-bound locus, Ptpn22. Our studies reveal that FOXP3 induces significant changes in the chromatin contacts between the Ptpn22 locus and other Foxp3-regulated genes, reflecting a mechanism by which FOXP3 reorganizes the genome architecture to coordinate the expression of its target genes. Our results suggest that FOXP3 mediates long-range chromatin interactions as part of its mechanisms to regulate specific gene expression in regulatory T cells. DNA binding by FOXP3 domain-swapped dimer suggests mechanisms of long-range chromosomal interactions.,Chen Y, Chen C, Zhang Z, Liu CC, Johnson ME, Espinoza CA, Edsall LE, Ren B, Zhou XJ, Grant SF, Wells AD, Chen L Nucleic Acids Res. 2015 Jan 7. pii: gku1373. PMID:25567984[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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