Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: An intrinsically disordered transcription activation domain alters the DNA binding affinity and specificity of NFκB p50/RelA Many transcription factors contain intrinsically disordered transcription activation domains (TADs), which mediate interactions with co-activators to activate transcription. Historically, DNA-binding domains and TADs have been considered as modular units, but recent studies have shown that TADs can influence DNA binding. We biophysically characterized the NF{kappa}B p50/RelA heterodimer including the RelA TAD and investigated the TADs influence on NF{kappa}B-DNA interactions. In solution the RelA TAD is disordered but compact, with helical tendency in two regions that interact with co-activators. The presence of the TAD increased the stoichiometry of NF{kappa}B-DNA complexes containing promoter DNA sequences with tandem {kappa}B recognition motifs by promoting the binding of NF{kappa}B dimers in excess of the number of {kappa}B sites. We measured the binding affinity of p50/RelA for DNA containing tandem {kappa}B sites and single {kappa}B sites. While the presence of the TAD enhanced the binding affinity of p50/RelA for all {kappa}B sequences tested, it increased the affinity for non-specific DNA sequences by over 10-fold, leading to an overall decrease in specificity for {kappa}B DNA sequences. Our results reveal a novel function of the RelA TAD in promoting binding to non-consensus DNA previously observed by in vivo studies of NF{kappa}B-DNA binding in response to strong inflammatory signals.
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The categories of this paper are: pharmacology
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The categories of this paper are: and
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The categories of this paper are: zoology
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The categories of this paper are: communication
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The categories of this paper are: developmental
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The categories of this paper are: genomics
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The categories of this paper are: toxicology
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The categories of this paper are: epidemiology
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The categories of this paper are: genetics
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The categories of this paper are: biophysics
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The categories of this paper are: cognition
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The categories of this paper are: ecology
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The categories of this paper are: education
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The categories of this paper are: neuroscience
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The categories of this paper are: biology
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The categories of this paper are: evolutionary