Journal Article

PUBDB-2025-02340

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Hierarchy in regulator interactions with distant transcriptional activation domains empowers rheostatic regulation

Due, A. D. ; Davey, N. E. ; Thomasen, F. E. ; Morffy, N. ; Prestel, A. ; Brakti, I. ; O'Shea, C. ; Strader, L. C. ; Lindorff-Larsen, K. ; Skriver, K. (Corresponding author) ; Kragelund, B. B. (Corresponding author)Extern*EMBL*

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/pro.70142  doi:10.3204/PUBDB-2025-02340

Abstract: Transcription factors carry long intrinsically disordered regions often containing multiple activation domains. Despite numerous recent high-throughput identifications and characterizations of activation domains, the interplay between sequence motifs, activation domains, and regulator binding in intrinsically disordered transcription factor regions remains unresolved. Here, we map sequence motifs and activation domains in an Arabidopsis thaliana NAC transcription factor clade, revealing that although sequence motifs and activation domains often coincide, no systematic overlap exists. Biophysical analyses using NMR spectroscopy show that the long intrinsically disordered region of senescence-associated transcription factor ANAC046 is devoid of residual structure. We identify two activation domain/sequence motif regions, one at each end that both bind a panel of six positive and negative regulator domains from biologically relevant regulators promiscuously. Binding affinities measured using isothermal titration calorimetry reveal a hierarchy for regulator binding of the two ANAC046 activation domain/sequence motif regions defining these as regulatory hotspots. Despite extensive dynamic intramolecular contacts along the disordered chain revealed using paramagnetic relaxation enhancement experiments and simulations, the regions remain uncoupled in binding. Together, the results imply rheostatic regulation by ANAC046 through concentration-dependent regulator competition, a mechanism likely mirrored in other transcription factors with distantly located activation domains.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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