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Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells

i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells....

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Autores principales: Zanin, Irene, Ruggiero, Emanuela, Nicoletto, Giulia, Lago, Sara, Maurizio, Ilaria, Gallina, Irene, Richter, Sara N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484731/
https://www.ncbi.nlm.nih.gov/pubmed/37528048
http://dx.doi.org/10.1093/nar/gkad626
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author Zanin, Irene
Ruggiero, Emanuela
Nicoletto, Giulia
Lago, Sara
Maurizio, Ilaria
Gallina, Irene
Richter, Sara N
author_facet Zanin, Irene
Ruggiero, Emanuela
Nicoletto, Giulia
Lago, Sara
Maurizio, Ilaria
Gallina, Irene
Richter, Sara N
author_sort Zanin, Irene
collection PubMed
description i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells. We mapped iMs in two human cell lines and recovered C-rich sequences that were confirmed to fold into iMs in vitro. We found that iMs in cells are mainly present at actively transcribing gene promoters, in open chromatin regions, they overlap with R-loops, and their abundance and distribution are specific to each cell type. iMs with both long and short C-tracts were recovered, further extending the relevance of iMs. By simultaneously mapping G-quadruplexes (G4s), which form at guanine-rich regions, and comparing the results with iMs, we proved that the two structures can form in independent regions; however, when both iMs and G4s are present in the same genomic tract, their formation is enhanced. iMs and G4s were mainly found at genes with low and high transcription rates, respectively. Our findings support the in vivo formation of iM structures and provide new insights into their interplay with G4s as new regulatory elements in the human genome.
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spelling pubmed-104847312023-09-09 Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells Zanin, Irene Ruggiero, Emanuela Nicoletto, Giulia Lago, Sara Maurizio, Ilaria Gallina, Irene Richter, Sara N Nucleic Acids Res NAR Breakthrough Article i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells. We mapped iMs in two human cell lines and recovered C-rich sequences that were confirmed to fold into iMs in vitro. We found that iMs in cells are mainly present at actively transcribing gene promoters, in open chromatin regions, they overlap with R-loops, and their abundance and distribution are specific to each cell type. iMs with both long and short C-tracts were recovered, further extending the relevance of iMs. By simultaneously mapping G-quadruplexes (G4s), which form at guanine-rich regions, and comparing the results with iMs, we proved that the two structures can form in independent regions; however, when both iMs and G4s are present in the same genomic tract, their formation is enhanced. iMs and G4s were mainly found at genes with low and high transcription rates, respectively. Our findings support the in vivo formation of iM structures and provide new insights into their interplay with G4s as new regulatory elements in the human genome. Oxford University Press 2023-08-02 /pmc/articles/PMC10484731/ /pubmed/37528048 http://dx.doi.org/10.1093/nar/gkad626 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle NAR Breakthrough Article
Zanin, Irene
Ruggiero, Emanuela
Nicoletto, Giulia
Lago, Sara
Maurizio, Ilaria
Gallina, Irene
Richter, Sara N
Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title_full Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title_fullStr Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title_full_unstemmed Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title_short Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
title_sort genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
topic NAR Breakthrough Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484731/
https://www.ncbi.nlm.nih.gov/pubmed/37528048
http://dx.doi.org/10.1093/nar/gkad626
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