ORBi: Smargiasso Nicolas - Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes

Reference : Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var ge...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology Physical, chemical, mathematical & earth Sciences : Chemistry
	To cite this reference:	http://hdl.handle.net/2268/20491

Title :	Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes
Language :	English
Author, co-author :	Smargiasso, Nicolas [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	Gabelica, Valérie [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	Damblon, Christian [Université de Liège - ULg > Département de chimie (sciences) > Chimie biologique structurale >]
	Rosu, Frédéric [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	De Pauw, Edwin [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	Teulade-Fichou, Marie-Paule [Institut Curie, Section Recherche, CNRS UMR176, Centre Universitaire Paris XI, Bat. 110, 91405 Orsay, France > > > >]
	Rowe, Jane A. [Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom > > > >]
	Claessens, Antoine [Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom > > > >]
Publication date :	2009
Journal title :	BMC Genomics
Publisher :	BioMed Central
Volume :	10
Pages :	362
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
e-ISSN :	1471-2164
Keywords :	[en] dna ; G-quadruplex ; mass spectrometry ; NMR ; electrospray ; noncovalent ; ligand ; spectroscopy
Abstract :	[en] Background. 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 Plasmodium falciparum genome, along with biophysical techniques to examine the physiological stability of P. falciparum PQS in vitro. Results. We identified 63 PQS in the non-telomeric regions of the P. falciparum clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the P. falciparum var genes (group B var genes). The var 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 var genes (UpsB-Q) to form stable Gquadruplex structures in vitro 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. Conclusions. This is the first demonstration of non-telomeric PQS in the genome of P. falciparum that form stable G-quadruplexes under physiological conditions in vitro. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of var genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family.
Research units :	Giga-Systems Biology and Chemical Biology ; Centre Interfacultaire d'Analyse des Résidus en Traces - CART
Funders :	Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/20491
DOI :	10.1186/1471-2164-10-362

File(s) associated to this reference

Fulltext file(s):

	File	Commentary	Version	Size	Access
Open access	2009-BMCgenomics-10-362.pdf		Author postprint	822.14 kB	View/Open

All documents in ORBi are protected by a user license.

Dspace v1.5