G-quadruplexes as novel cis-elements controlling transcription during embryonic development

G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional r...

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Bibliographic Details
Published in:Nucleic acids research 2016-05, Vol.44 (9), p.4163-4173
Main Authors: David, Aldana P, Margarit, Ezequiel, Domizi, Pablo, Banchio, Claudia, Armas, Pablo, Calcaterra, Nora B
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Line, Tumor
Collagen Type II - genetics
Collagen Type II - metabolism
Danio rerio
DNA, Single-Stranded
Embryo, Nonmammalian - metabolism
G-Quadruplexes
Gene Expression Regulation, Developmental
Gene regulation, Chromatin and Epigenetics
Humans
Mice
Promoter Regions, Genetic
Simian virus 40
Transcription, Genetic
Zebrafish - embryology
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - genetics
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Summary:G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during vertebrate embryonic development has not yet been addressed. Here, we performed an in silico search to find conserved putative G-quadruplex sequences (PQSs) within proximal promoter regions of human, mouse and zebrafish developmental genes. Among the PQSs able to fold in vitro as G-quadruplex, those present in nog3, col2a1 and fzd5 promoters were selected for further studies. In cellulo studies revealed that the selected G-quadruplexes affected the transcription of luciferase controlled by the SV40 nonrelated promoter. G-quadruplex disruption in vivo by microinjection in zebrafish embryos of either small ligands or DNA oligonucleotides complementary to the selected PQSs resulted in lower transcription of the targeted genes. Moreover, zebrafish embryos and larvae phenotypes caused by the presence of complementary oligonucleotides fully resembled those ones reported for nog3, col2a1 and fzd5 morphants. To our knowledge, this is the first work revealing in vivo the role of conserved G-quadruplexes in the embryonic development, one of the most regulated processes of the vertebrates biology.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkw011