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Nucleic Acids Research Advance Access published online on February 11, 2009
Nucleic Acids Research, doi:10.1093/nar/gkn1076
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Evidence of genome-wide G4 DNA-mediated gene expression in human cancer cells

Anjali Verma1, Vinod Kumar Yadav2, Richa Basundra1, Akinchan Kumar1 and Shantanu Chowdhury1,2,*

1Proteomics and Structural Biology Unit and 2G. N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India

*To whom correspondence should be addressed. Tel: +91 11 2766 6157; Fax: +91 11 2766 7471; Email: shantanuc{at}igib.res.in

Received November 23, 2008. Revised December 22, 2008. Accepted December 22, 2008.

Guanine-rich DNA of a particular sequence adopts four-stranded structural forms known as G-quadruplex or G4 DNA. Though in vitro formation of G4 DNA is known for several years, in vivo presence of G4 DNA was only recently noted in eukaryote telomeres. Recent bioinformatics analyses showing prevalence of G4 DNA within promoters of human and related species seems to implicate G4 DNA in a genome-wide cis-regulatory role. Herein we demonstrate that G4 DNA may present regulatory sites on a genome-wide scale by showing widespread effect on gene expression in response to the established intracellular G4 DNA-binding ligands. This is particularly relevant to genes that harbor conserved potential G4 DNA (PG4 DNA) forming sequence across human, mouse and rat promoters of orthologous genes. Genes with conserved PG4 DNA in promoters show co-regulated expression in 79 human and 61 mouse normal tissues (z-score > 3.5; P < 0.0001). Conservation of G4 DNA across related species also emphasizes the biological importance of G4 DNA and its role in transcriptional regulation of genes; shedding light on a relatively novel mechanism of regulation of gene expression in eukaryotes.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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