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G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin

G-quadruplexes (G4s) are nucleic acid secondary structures detected within human chromosomes, that cluster at gene promoters and enhancers. This suggests that G4s may play specific roles in the regulation of gene expression. Within a distinct subgroup of G-rich domains, the formation of two or more...

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Autores principales: Cozzaglio, Marta, Ceschi, Silvia, Groaz, Elisabetta, Sturlese, Mattia, Sissi, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520404/
https://www.ncbi.nlm.nih.gov/pubmed/36186582
http://dx.doi.org/10.3389/fchem.2022.1008075
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author Cozzaglio, Marta
Ceschi, Silvia
Groaz, Elisabetta
Sturlese, Mattia
Sissi, Claudia
author_facet Cozzaglio, Marta
Ceschi, Silvia
Groaz, Elisabetta
Sturlese, Mattia
Sissi, Claudia
author_sort Cozzaglio, Marta
collection PubMed
description G-quadruplexes (G4s) are nucleic acid secondary structures detected within human chromosomes, that cluster at gene promoters and enhancers. This suggests that G4s may play specific roles in the regulation of gene expression. Within a distinct subgroup of G-rich domains, the formation of two or more adjacent G4 units (G4-repeats) is feasible. Recently it was shown that Vimentin, a protein highly expressed within mesenchymal cells, selectively recognizes these arrangements. Putative G4-repeats have been searched within the human gene proximal promoters by the bioinformatics tool QPARSE and they resulted to be enriched at genes related to epithelial-to-mesenchymal transition (EMT). This suggested that Vimentin binding at these sites might be relevant for the maintenance of the mesenchymal phenotype. Among all the identified sequences, in the present study we selected the one located within the promoter of the TEAD4 oncogene. TEAD4 codifies for a transcriptional enhancer factor, TEAD4, that actively promotes EMT, supporting, cell proliferation and migration. Moreover, in colorectal cancer cells TEAD4 directly enhances the expression of Vimentin. Thus, the possible interaction of Vimentin with TEAD4 promoter could highlight a positive feedback loop between these two factors, associated to important tumor metastasis related events. Here, we exploited spectroscopic and electrophoretic measurements under different conditions to address the folding behavior of the selected sequence. This allowed us to validate the folding of TEAD4 promoter into a G4-repeat able to interact with Vimentin.
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spelling pubmed-95204042022-09-30 G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin Cozzaglio, Marta Ceschi, Silvia Groaz, Elisabetta Sturlese, Mattia Sissi, Claudia Front Chem Chemistry G-quadruplexes (G4s) are nucleic acid secondary structures detected within human chromosomes, that cluster at gene promoters and enhancers. This suggests that G4s may play specific roles in the regulation of gene expression. Within a distinct subgroup of G-rich domains, the formation of two or more adjacent G4 units (G4-repeats) is feasible. Recently it was shown that Vimentin, a protein highly expressed within mesenchymal cells, selectively recognizes these arrangements. Putative G4-repeats have been searched within the human gene proximal promoters by the bioinformatics tool QPARSE and they resulted to be enriched at genes related to epithelial-to-mesenchymal transition (EMT). This suggested that Vimentin binding at these sites might be relevant for the maintenance of the mesenchymal phenotype. Among all the identified sequences, in the present study we selected the one located within the promoter of the TEAD4 oncogene. TEAD4 codifies for a transcriptional enhancer factor, TEAD4, that actively promotes EMT, supporting, cell proliferation and migration. Moreover, in colorectal cancer cells TEAD4 directly enhances the expression of Vimentin. Thus, the possible interaction of Vimentin with TEAD4 promoter could highlight a positive feedback loop between these two factors, associated to important tumor metastasis related events. Here, we exploited spectroscopic and electrophoretic measurements under different conditions to address the folding behavior of the selected sequence. This allowed us to validate the folding of TEAD4 promoter into a G4-repeat able to interact with Vimentin. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520404/ /pubmed/36186582 http://dx.doi.org/10.3389/fchem.2022.1008075 Text en Copyright © 2022 Cozzaglio, Ceschi, Groaz, Sturlese and Sissi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Cozzaglio, Marta
Ceschi, Silvia
Groaz, Elisabetta
Sturlese, Mattia
Sissi, Claudia
G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title_full G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title_fullStr G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title_full_unstemmed G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title_short G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin
title_sort g-quadruplexes formation within the promoter of tead4 oncogene and their interaction with vimentin
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520404/
https://www.ncbi.nlm.nih.gov/pubmed/36186582
http://dx.doi.org/10.3389/fchem.2022.1008075
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