DNA facilitates heterodimerization between human transcription factors FoxP1 and FoxP2 by increasing their conformational flexibility

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dc.contributor.authorConuecar, Ricardo
dc.contributor.authorAsela, Isabel
dc.contributor.authorRivera, Maira
dc.contributor.authorGalaz-Davison, Pablo
dc.contributor.authorGonzalez-Higueras, Jorge
dc.contributor.authorHamilton, George L.
dc.contributor.authorEngelberger, Felipe
dc.contributor.authorRamirez-Sarmiento, Cesar A.
dc.contributor.authorBabul, Jorge
dc.contributor.authorSanabria, Hugo
dc.contributor.authorMedina, Exequiel
dc.date.accessioned2025-01-20T20:07:35Z
dc.date.available2025-01-20T20:07:35Z
dc.date.issued2023
dc.description.abstractTranscription factors regulate gene expression by binding to DNA. They have disordered regions and specific DNA-binding domains. Binding to DNA causes structural changes, including folding and interactions with other molecules. The FoxP subfamily of transcription factors in humans is unique because they can form heterotypic interactions without DNA. However, it is unclear how they form heterodimers and how DNA binding affects their function. We used computational and experimental methods to study the structural changes in FoxP1's DNA-binding domain when it forms a heterodimer with FoxP2. We found that FoxP1 has complex and diverse conformational dynamics, transitioning between compact and extended states. Surprisingly, DNA binding increases the flexibility of FoxP1, contrary to the typical folding-upon-binding mechanism. In addition, we observed a 3-fold increase in the rate of heterodimerization after FoxP1 binds to DNA. These findings emphasize the importance of structural flexibility in promoting heterodimerization to form transcriptional complexes.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.isci.2023.107228
dc.identifier.eissn2589-0042
dc.identifier.urihttps://doi.org/10.1016/j.isci.2023.107228
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91821
dc.identifier.wosidWOS:001049249600001
dc.issue.numero7
dc.language.isoen
dc.revistaIscience
dc.rightsacceso restringido
dc.subject.ods15 Life on Land
dc.subject.odspa15 Vida de ecosistemas terrestres
dc.titleDNA facilitates heterodimerization between human transcription factors FoxP1 and FoxP2 by increasing their conformational flexibility
dc.typeartículo
dc.volumen26
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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