Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites

0541387 - BFÚ 2021 RIV US eng J - Journal Article
Gazanion, E. - Lacroix, L. - Alberti, P. - Gurung, P. - Wein, S. - Cheng, M. - Mergny, Jean-Louis - Gomes, A. R. - Lopez-Rubio, J.J.
Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites.
PLoS Genetics. Roč. 16, č. 7 (2020), č. článku e1008917. ISSN 1553-7404. E-ISSN 1553-7404
R&D Projects: GA MŠMT EF15_003/0000477
Institutional support: RVO:68081707
Keywords : mutually exclusive expression * plasmodium-falciparum * virulence genes * antigenic variation * small-molecule * dna
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 5.917, year: 2020
Method of publishing: Open access
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008917

Mechanisms of transcriptional control in malaria parasites are still not fully understood. The positioning patterns of G-quadruplex (G4) DNA motifs in the parasite's AT-rich genome, especially within thevargene family which encodes virulence factors, and in the vicinity of recombination hotspots, points towards a possible regulatory role of G4 in gene expression and genome stability. Here, we carried out the most comprehensive genome-wide survey, to date, of G4s in thePlasmodium falciparumgenome using G4Hunter, which identifies G4 forming sequences (G4FS) considering their G-richness and G-skewness. We show an enrichment of G4FS in nucleosome-depleted regions and in the first exon ofvargenes, a pattern that is conserved within the closely relatedLaverania Plasmodiumparasites. Under G4-stabilizing conditions,i.e., following treatment with pyridostatin (a high affinity G4 ligand), we show that abona fideG4 found in the non-coding strand ofvarpromoters modulates reporter gene expression. Furthermore, transcriptional profiling of pyridostatin-treated parasites, shows large scale perturbations, with deregulation affecting for instance the ApiAP2 family of transcription factors and genes involved in ribosome biogenesis. Overall, our study highlights G4s as important DNA secondary structures with a role inPlasmodiumgene expression regulation, sub-telomeric recombination andvargene biology.
Permanent Link: http://hdl.handle.net/11104/0318946