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CNBP controls transcription by unfolding DNA G-quadruplex structures
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Edité par CCSD ; Oxford University Press -
International audience. 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 ascis-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 presentdata revealing that CNBP acts in vitro as a G4-unfolding protein over a tetramolecular G4 formed by the TG4 T oligonucleotide, as well as over the G4 folded in the promoters of several oncogenes. CNBP depletionin 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 unfoldedin 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 un-winding. Our results shed light on the mechanismsunderlying CNBP way of action, as well as reinforce the notion about the existence and function of G4sin whole living organisms.
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