DNA controls the dimerization of the human FoxP1 forkhead domain

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dc.contributor.authorKolimi, Narendar
dc.contributor.authorBallard, Jake
dc.contributor.authorPeulen, Thomas
dc.contributor.authorGoutam, Rajen
dc.contributor.authorDuffy III, Francis X.
dc.contributor.authorRamirez-Sarmiento, Cesar A.
dc.contributor.authorBabul, Jorge
dc.contributor.authorMedina, Exequiel
dc.contributor.authorSanabria, Hugo
dc.date.accessioned2025-01-20T16:09:19Z
dc.date.available2025-01-20T16:09:19Z
dc.date.issued2024
dc.description.abstractTranscription factors (TFs) regulate gene expression by binding to specific DNA sequences and gating access to genes. Even when the binding of TFs and their cofactors to DNA is reversible, indicating a reversible control of gene expression, there is little knowledge about the molecular effect DNA has on TFs. Using single -molecule multiparameter fluorescence spectroscopy, molecular dynamics simulations, and biochemical assays, we find that the monomeric form of the forkhead (FKH) domain of the human FoxP1 behaves as a disordered protein and increases its folded population when it dimerizes. Notably, DNA binding promotes a disordered FKH dimer bound to DNA, negatively controlling the stability of the dimeric FoxP1:DNA complex. The DNA -mediated reversible regulation on FKH dimers suggests that FoxP1-dependent gene suppression is unstable, and it must require the presence of other dimerization domains or cofactors to revert the negative impact exerted by the DNA.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.xcrp.2024.101854
dc.identifier.eissn2666-3864
dc.identifier.urihttps://doi.org/10.1016/j.xcrp.2024.101854
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90146
dc.identifier.wosidWOS:001258465100001
dc.issue.numero3
dc.language.isoen
dc.revistaCell reports physical science
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDNA controls the dimerization of the human FoxP1 forkhead domain
dc.typeartículo
dc.volumen5
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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