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000626391 1001_ $$0P:(DE-HGF)0$$aDelaforge, Elise$$b0
000626391 245__ $$aAllovalent scavenging of activation domains in the transcription factor ANAC013 gears transcriptional regulation
000626391 260__ $$aOxford$$bOxford Univ. Press$$c2025
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000626391 520__ $$aTranscriptional regulation involves interactions between transcription factors, coregulators, and DNA. Intrinsic disorder is a major player in this regulation, but mechanisms driven by disorder remain elusive. Here, we address molecular communication within the stress-regulating Arabidopsis thaliana transcription factor ANAC013. Through high-throughput screening of ANAC013 for transcriptional activation activity, we identify three activation domains within its C-terminal intrinsically disordered region. Two of these overlap with acidic islands and form dynamic interactions with the DNA-binding domain and are released, not only upon binding of target promoter DNA, but also by nonspecific DNA. We show that independently of DNA binding, the RST (RCD--SRO--TAF4) domain of the negative regulator RCD1 (Radical-induced Cell Death1) scavenges the two acidic activation domains positioned vis-à-vis through allovalent binding, leading to dynamic occupation at enhanced affinity. We propose an allovalency model for transcriptional regulation, where sequentially close activation domains in both DNA-bound and DNA-free states allow for efficient regulation. The model is likely relevant for many transcription factor systems, explaining the functional advantage of carrying sequentially close activation domains.
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000626391 7001_ $$0P:(DE-HGF)0$$aDue, Amanda D$$b1
000626391 7001_ $$00000-0002-3412-4242$$aTheisen, Frederik Friis$$b2
000626391 7001_ $$aMorffy, Nicolas$$b3
000626391 7001_ $$aO’Shea, Charlotte$$b4
000626391 7001_ $$aBlackledge, Martin$$b5
000626391 7001_ $$aStrader, Lucia C$$b6
000626391 7001_ $$0P:(DE-HGF)0$$aSkriver, Karen$$b7$$eCorresponding author
000626391 7001_ $$0P:(DE-HGF)0$$aKragelund, Birthe B$$b8$$eCorresponding author
000626391 773__ $$0PERI:(DE-600)2205588-5$$a10.1093/nar/gkaf065$$gVol. 53, no. 4, p. gkaf065$$n4$$pgkaf065$$tNucleic acids symposium series$$v53$$x0305-1048$$y2025
000626391 8564_ $$uhttps://academic.oup.com/nar/article/53/4/gkaf065/8008525
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