In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells

Pavlína Víšková, Eva Ištvánková, Jan Ryneš, Šimon Džatko, Tomáš Loja, Martina Lenarčič Živković, Riccardo Rigo, Roberto El-Khoury, Israel Serrano-Chacón, Masad J. Damha, Carlos González, Jean-Louis Mergny, Silvie Foldynová-Trantírková () and Lukáš Trantírek ()
Additional contact information
Pavlína Víšková: Masaryk University
Eva Ištvánková: Masaryk University
Jan Ryneš: Masaryk University
Šimon Džatko: Masaryk University
Tomáš Loja: Masaryk University
Martina Lenarčič Živković: Masaryk University
Riccardo Rigo: Masaryk University
Roberto El-Khoury: McGill University
Israel Serrano-Chacón: CSIC
Masad J. Damha: McGill University
Carlos González: CSIC
Jean-Louis Mergny: Czech Academy of Sciences
Silvie Foldynová-Trantírková: Masaryk University
Lukáš Trantírek: Masaryk University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C. Our findings show that iMFPS displaying pHT 7 appear as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) reveals that cell cycle-dependent iM formation has a dual origin, and iM formation concerns only a tiny fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46221-y 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:15:y:2024:i:1:d:10.1038_s41467-024-46221-y

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

DOI: 10.1038/s41467-024-46221-y

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 ().