4WK8

FOXP3 forms a domain-swapped dimer to bridge DNA

Summary for 4WK8

• Entry DOI: 10.2210/pdb4wk8/pdb
• Descriptor: DNA (5'-D(*TP*TP*AP*GP*GP*AP*AP*AP*AP*TP*TP*TP*GP*TP*TP*TP*CP*AP*TP*AP*G)-3'), DNA (5'-D(*AP*AP*CP*TP*AP*TP*GP*AP*AP*AP*CP*AP*AP*AP*TP*TP*TP*TP*CP*CP*T)-3'), Forkhead box protein P3 (3 entities in total)
• Functional Keywords: foxp3, regulatory t cells, dna bridging, transcription regulation, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 33045.87

Authors

Chen, Y.,Chen, L. (deposition date: 2014-10-01, release date: 2015-01-21, Last modification date: 2023-12-27)

Primary citation

Chen, Y.,Chen, C.,Zhang, Z.,Liu, C.C.,Johnson, M.E.,Espinoza, C.A.,Edsall, L.E.,Ren, B.,Zhou, X.J.,Grant, S.F.,Wells, A.D.,Chen, L.
DNA binding by FOXP3 domain-swapped dimer suggests mechanisms of long-range chromosomal interactions.
Nucleic Acids Res., 43:1268-1282, 2015

PubMed Abstract: FOXP3 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.

PubMed: 25567984
DOI: 10.1093/nar/gku1373

Experimental method

X-RAY DIFFRACTION (3.4006 Å)