Putative DNA G-quadruplex formation within the promoters of <it>Plasmodium falciparum var </it>genes

• Main Authors: Rowe J, Teulade-Fichou Marie-Paule, De Pauw Edwin, Rosu Frédéric, Damblon Christian, Gabelica Valérie, Smargiasso Nicolas, Claessens Antoine
• Format: Article
• Language: English
• Published: BMC 2009-08-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/10/362

<p>Abstract</p> <p>Background</p> <p>Guanine-rich nucleic acid sequences are capable of folding into an intramolecular four-stranded structure called a G-quadruplex. When found in gene promoter regions, G-quadruplexes can downregulate gene expression, possibly by blocking the transcriptional machinery. Here we have used a genome-wide bioinformatic approach to identify Putative G-Quadruplex Sequences (PQS) in the <it>Plasmodium falciparum </it>genome, along with biophysical techniques to examine the physiological stability of <it>P. falciparum </it>PQS <it>in vitro</it>.</p> <p>Results</p> <p>We identified 63 PQS in the non-telomeric regions of the <it>P. falciparum </it>clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the <it>P. falciparum var </it>genes (group B <it>var </it>genes). The <it>var </it>gene family encodes PfEMP1, the parasite's major variant antigen and adhesin expressed at the surface of infected erythrocytes, that plays a key role in malaria pathogenesis and immune evasion. The ability of the PQS found in the upstream regions of group B <it>var </it>genes (UpsB-Q) to form stable G-quadruplex structures <it>in vitro </it>was confirmed using ¹H NMR, circular dichroism, UV spectroscopy, and thermal denaturation experiments. Moreover, the synthetic compound BOQ1 that shows a higher affinity for DNA forming quadruplex rather than duplex structures was found to bind with high affinity to the UpsB-Q.</p> <p>Conclusion</p> <p>This is the first demonstration of non-telomeric PQS in the genome of <it>P. falciparum </it>that form stable G-quadruplexes under physiological conditions <it>in vitro</it>. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of <it>var </it>genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family.</p>