TY  - INPR
A1  - Bjarnason, Sveinn
A1  - McIvor, Jordan A. P.
A1  - Prestel, Andreas
A1  - Demény, Kinga S.
A1  - Bullerjahn, Jakob Tómas
A1  - Kragelund, Birthe B.
A1  - Mercadante, Davide
A1  - Heidarsson, Pétur O.
T1  - DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2
T2  - bioRxiv
N2  - More than 1600 human transcription factors orchestrate the transcriptional machinery to control gene expression and cell fate. Their function is conveyed through intrinsically disordered regions (IDRs) containing activation or repression domains but lacking quantitative structural ensemble models prevents their mechanistic decoding. Here we integrate single-molecule FRET and NMR spectroscopy with molecular simulations showing that DNA binding can lead to complex changes in the IDR ensemble and accessibility. The C-terminal IDR of pioneer factor Sox2 is highly disordered but its conformational dynamics are guided by weak and dynamic charge interactions with the folded DNA binding domain. Both DNA and nucleosome binding induce major rearrangements in the IDR ensemble without affecting DNA binding affinity. Remarkably, interdomain interactions are redistributed in complex with DNA leading to variable exposure of two activation domains critical for transcription. Charged intramolecular interactions allowing for dynamic redistributions may be common in transcription factors and necessary for sensitive tuning of structural ensembles.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74465
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-744651
UR  - https://www.biorxiv.org/content/10.1101/2023.06.16.545083v1
IS  - 2023.06.16.545083 Version 1
PB  - bioRxiv
ER  -