Nucleic Acids Research Advance Access originally published online on September 16, 2009
Nucleic Acids Research 2009 37(20):6784-6798; doi:10.1093/nar/gkp710
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Nucleic Acids Research, 2009, Vol. 37, No. 20 6784-6798
© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Genome-wide colonization of gene regulatory elements by G4 DNA motifs
1State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing, 100193, P.R. China and 2Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
*To whom correspondence should be addressed. Tel: +86 10 62733323; Fax: +86 10 62733904; Email: ninglcau{at}cau.edu.cn
Received April 3, 2009. Revised July 13, 2009. Accepted August 11, 2009.
G-quadruplex (or G4 DNA), a stable four-stranded structure found in guanine-rich regions, is implicated in the transcriptional regulation of genes involved in growth and development. Previous studies on the role of G4 DNA in gene regulation mostly focused on genomic regions proximal to transcription start sites (TSSs). To gain a more comprehensive understanding of the regulatory role of G4 DNA, we examined the landscape of potential G4 DNA (PG4Ms) motifs in the human genome and found that G4 motifs, not restricted to those found in the TSS-proximal regions, are bias toward gene-associated regions. Significantly, analyses of G4 motifs in seven types of well-known gene regulatory elements revealed a constitutive enrichment pattern and the clusters of G4 motifs tend to be colocalized with regulatory elements. Considering our analysis from a genome evolutionary perspective, we found evidence that the occurrence and accumulation of certain progenitors and canonical G4 DNA motifs within regulatory regions were progressively favored by natural selection. Our results suggest that G4 DNA motifs are ‘colonized’ in regulatory regions, supporting a likely genome-wide role of G4 DNA in gene regulation. We hypothesize that G4 DNA is a regulatory apparatus situated in regulatory elements, acting as a molecular switch that can modulate the role of the host functional regions, by transition in DNA structure.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.