Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA

Tuan Nguyen, Sai Li, Jeremy T-H Chang, John W. Watters, Htet Ng, Adewola Osunsade, Yael David and Shixin Liu ()
Additional contact information
Tuan Nguyen: The Rockefeller University
Sai Li: The Rockefeller University
Jeremy T-H Chang: The Rockefeller University
John W. Watters: The Rockefeller University
Htet Ng: The Rockefeller University
Adewola Osunsade: Memorial Sloan Kettering Cancer Center
Yael David: Memorial Sloan Kettering Cancer Center
Shixin Liu: The Rockefeller University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Biomolecular condensation constitutes an emerging mechanism for transcriptional regulation. Recent studies suggest that the co-condensation between transcription factors (TFs) and DNA can generate mechanical forces driving genome rearrangements. However, the reported forces generated by protein-DNA co-condensation are typically below one piconewton (pN), questioning its physiological significance. Moreover, the force-generating capacity of these condensates in the chromatin context remains unknown. Here, we show that Sox2, a nucleosome-binding pioneer TF, forms co-condensates with DNA and generates forces up to 7 pN, exerting considerable mechanical tension on DNA strands. We find that the disordered domains of Sox2 are required for maximum force generation but not for condensate formation. Furthermore, we show that nucleosomes dramatically attenuate the mechanical stress exerted by Sox2 by sequestering it from coalescing on bare DNA. Our findings reveal that TF-mediated DNA condensation can exert significant mechanical stress on the genome which can nonetheless be attenuated by the chromatin architecture.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31738-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31738-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31738-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().