Cellular nucleic acid binding protein (Cnbp) regulates zebrafish noggin 3 transcription through unfolding of a conserved G-quadruplex in its promoter.

DAVID, ALDANA P; ARMAS PABLO; CALCATERRA NORA; ANDREA M.J. WEINER

Buenos Aires

Congreso; LASDB Meeting 2019; 2019

Latin American Society for Developmental Biology

Guanine quadruplexes (G-quadruplexes or G4) are non-canonical DNA and RNA secondary structures involved in different aspects of gene expression regulation. Through bioinformatic analysis of zebrafish, mouse and human genomes we identified several genes involved in development that contain conserved G4s in their proximal promoter regions (PPRs, -1000 bp). Among them, the G4 present in the PPR of noggin 3 (nog3) gene was shown to function as transcriptional enhancer in cultured cells and in vivo during zebrafish development (David et al., Nucleic Acids Res. 2016, 44(9): 4163-73). The main role of nog3 gene during zebrafish development is in craniofacial chondrogenesis. On the other hand, cellular nucleic acid binding protein (Cnbp) is involved in craniofacial development, participating in the formation cartilaginous structures derived from neural crest cells. Cnbp is capable of unfolding G4s and through this activity controlling gene expression. Therefore, we assessed the role of Cnbp in the G4-mediated nog3 transcriptional regulation. In vitro experiments indicated that Cnbp is able to specifically bind and unfold the G4 present in nog3 PPR. In agreement with this biochemical function, experiments in cultured cells and in vivo during zebrafish development showed that CNBP is able to repress nog3 transcription. Results suggest that Cnbp function in craniofacial development may be explained, at least in part, by its unfolding activity on the G4 that controls nog3 transcription.