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


Autoři: Elodie Gazanion aff001;  Laurent Lacroix aff002;  Patrizia Alberti aff003;  Pratima Gurung aff004;  Sharon Wein aff004;  Mingpan Cheng aff005;  Jean-Louis Mergny aff005;  Ana Rita Gomes aff004;  Jose-Juan Lopez-Rubio aff001
Působiště autorů: MIVEGEC UMR IRD 224, CNRS 5290, Montpellier University, Montpellier, France aff001;  IBENS, Ecole Normale Supérieure, CNRS, Inserm, PSL Research University, Paris, France aff002;  "Structure and Instability of Genomes" laboratory, Muséum National d'Histoire Naturelle (MNHN), Inserm U1154, CNRS UMR 7196, Paris, France aff003;  Laboratory of Pathogen-Host Interactions (LPHI), UMR5235, CNRS, Montpellier University, Montpellier, France aff004;  ARNA Laboratory, IECB, CNRS UMR5320, INSERM U1212, Bordeaux University, Pessac, France aff005;  Institute of Biophysics of the Czech Academy of Sciences, Czech Republic aff006;  Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, France aff007
Vyšlo v časopise: Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites. PLoS Genet 16(7): e1008917. doi:10.1371/journal.pgen.1008917
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008917

Souhrn

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 the var gene 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 the Plasmodium falciparum genome 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 of var genes, a pattern that is conserved within the closely related Laverania Plasmodium parasites. Under G4-stabilizing conditions, i.e., following treatment with pyridostatin (a high affinity G4 ligand), we show that a bona fide G4 found in the non-coding strand of var promoters 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 in Plasmodium gene expression regulation, sub-telomeric recombination and var gene biology.

Klíčová slova:

Gene expression – Gene regulation – Genome analysis – Introns – Malarial parasites – Plasmodium – Plasmodium falciparum – Sequence motif analysis


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