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In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells
P. Víšková, E. Ištvánková, J. Ryneš, Š. Džatko, T. Loja, ML. Živković, R. Rigo, R. El-Khoury, I. Serrano-Chacón, MJ. Damha, C. González, JL. Mergny, S. Foldynová-Trantírková, L. Trantírek
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
CZ.02.2.69/0.0/0.0/20_079/0017045
Ministerstvo Školství, Mládeže a Tělovýchovy (Ministry of Education, Youth and Sports)
CZ.02.1.01/0.0/0.0/15_003/0000477
Ministerstvo Školství, Mládeže a Tělovýchovy (Ministry of Education, Youth and Sports)
Discovery Grant
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
ANR-21-CE44-0005-01
Agence Nationale de la Recherche (French National Research Agency)
Free Medical Journals od 2010
Nature Open Access od 2010-12-01
PubMed Central od 2012
Europe PubMed Central od 2012
ProQuest Central od 2010-01-01
Open Access Digital Library od 2015-01-01
Open Access Digital Library od 2015-01-01
Medline Complete (EBSCOhost) od 2012-11-01
Health & Medicine (ProQuest) od 2010-01-01
ROAD: Directory of Open Access Scholarly Resources od 2010
Odkazy
PubMed
38443388
DOI
10.1038/s41467-024-46221-y
Knihovny.cz E-zdroje
- MeSH
- azidy * MeSH
- benzazepiny * MeSH
- DNA MeSH
- HeLa buňky MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- protilátky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with 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.
Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic
Centre for Advanced Materials Application Slovak Academy of Sciences 845 11 Bratislava Slovakia
Department of Chemistry McGill University Montreal QC H3A0B8 Canada
Institute of Biophysics Czech Academy of Sciences Brno 612 00 Czech Republic
Instituto de Química Física 'Blas Cabrera' CSIC C Serrano 119 28006 Madrid Spain
National Centre for Biomolecular Research Masaryk University 625 00 Brno Czech Republic
Pharmaceutical and Pharmacological Sciences Department University of Padova 35131 Padova Italy
Slovenian NMR Centre National Institute of Chemistry SI 1000 Ljubljana Slovenia
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- $a 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 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with 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.
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