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• W2143365357 endingPage "9591" @default.
• W2143365357 startingPage "9574" @default.
• W2143365357 abstract "Many proteins of the Rel family can act as both transcriptional activators and repressors. However, mechanism that discerns the ‘activator/repressor’ functions of Rel-proteins such as Dorsal ( Drosophila homologue of mammalian NFκB) is not understood. Using genomic, biophysical and biochemical approaches, we demonstrate that the underlying principle of this functional specificity lies in the ‘sequence-encoded structure’ of the κB- DNA. We show that Dorsal-binding motifs exist in distinct activator and repressor conformations. Molecular dynamics of DNA-Dorsal complexes revealed that repressor κB -motifs typically have A-tract and flexible conformation that facilitates interaction with co-repressors. Deformable structure of repressor motifs, is due to changes in the hydrogen bonding in A:T pair in the ‘A-tract’ core. The sixth nucleotide in the nonameric κB -motif, ‘A’ (A 6 ) in the repressor motifs and ‘T’ (T 6 ) in the activator motifs, is critical to confer this functional specificity as A 6 → T 6 mutation transformed flexible repressor conformation into a rigid activator conformation. These results highlight that ‘sequence encoded κB DNA-geometry’ regulates gene expression by exerting allosteric effect on binding of Rel proteins which in turn regulates interaction with co-regulators. Further, we identified and characterized putative repressor motifs in Dl-target genes, which can potentially aid in functional annotation of Dorsal gene regulatory network." @default.
• W2143365357 created "2016-06-24" @default.
• W2143365357 creator A5028306738 @default.
• W2143365357 creator A5077289947 @default.
• W2143365357 creator A5081742470 @default.
• W2143365357 date "2011-09-02" @default.
• W2143365357 modified "2023-10-17" @default.
• W2143365357 title "Role of sequence encoded κB DNA geometry in gene regulation by Dorsal" @default.
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• W2143365357 doi "https://doi.org/10.1093/nar/gkr672" @default.
• W2143365357 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3239199" @default.
• W2143365357 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21890896" @default.
• W2143365357 hasPublicationYear "2011" @default.
• W2143365357 type Work @default.

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