PUBLICATION

CNBP controls transcription by unfolding DNA G-quadruplex structures

Authors
David, A.P., Pipier, A., Pascutti, F., Binolfi, A., J Weiner, A.M., Challier, E., Heckel, S., Calsou, P., Gomez, D., Calcaterra, N.B., Armas, P.
ID
ZDB-PUB-190621-6
Date
2019
Source
Nucleic acids research   47(15): 7901-7913 (Journal)
Registered Authors
Calcaterra, Nora
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism
  • DNA/chemistry*
  • DNA/genetics
  • DNA/metabolism
  • Embryo, Nonmammalian
  • G-Quadruplexes*
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • HeLa Cells
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism
  • Transcription, Genetic*
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
31219592 Full text @ Nucleic Acids Res.
Abstract
Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4). Experimental evidences suggest that G4-DNA surrounding transcription start sites act as cis-regulatory elements by either stimulating or inhibiting gene transcription. Therefore, proteins able to target and regulate specific G4 formation/unfolding are crucial for G4-mediated transcriptional control. Here we present data revealing that CNBP acts in vitro as a G4-unfolding protein over a tetramolecular G4 formed by the TG4T oligonucleotide, as well as over the G4 folded in the promoters of several oncogenes. CNBP depletion in cellulo led to a reduction in the transcription of endogenous KRAS, suggesting a regulatory role of CNBP in relieving the transcriptional abrogation due to G4 formation. CNBP activity was also assayed over the evolutionary conserved G4 enhancing the transcription of NOGGIN (NOG) developmental gene. CNBP unfolded in vitro NOG G4 and experiments performed in cellulo and in vivo in developing zebrafish showed a repressive role of CNBP on the transcription of this gene by G4 unwinding. Our results shed light on the mechanisms underlying CNBP way of action, as well as reinforce the notion about the existence and function of G4s in whole living organisms.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping