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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....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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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. |
format | Online Article Text |
id | pubmed-10484731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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