TY - JOUR
AU - Delaforge, Elise
AU - Due, Amanda D
AU - Theisen, Frederik Friis
AU - Morffy, Nicolas
AU - O’Shea, Charlotte
AU - Blackledge, Martin
AU - Strader, Lucia C
AU - Skriver, Karen
AU - Kragelund, Birthe B
TI - Allovalent scavenging of activation domains in the transcription factor ANAC013 gears transcriptional regulation
JO - Nucleic acids symposium series
VL - 53
IS - 4
SN - 0305-1048
CY - Oxford
PB - Oxford Univ. Press
M1 - PUBDB-2025-01383
SP - gkaf065
PY - 2025
N1 - ISSN 1362-4962 not unique: **2 hits**.
AB - Transcriptional 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.
LB - PUB:(DE-HGF)16
UR - <Go to ISI:>//WOS:001417619200001
DO - DOI:10.1093/nar/gkaf065
UR - https://bib-pubdb1.desy.de/record/626391
ER -