Nucleic Acids Research Advance Access originally published online on January 10, 2008
Nucleic Acids Research 2008 36(4):1321-1333; doi:10.1093/nar/gkm1138
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2008, Vol. 36, No. 4 1321-1333
© 2008 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.
Genomics |
Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes
1Molecular and Cellular Biology Graduate Program, University of Washington and 2Department of Immunology and Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195-7650, USA
*To whom correspondence should be addressed. Tel: +1 206 221 6876; Fax: +1 206 221 6781; Email: maizels{at}u.washington.edu
Received November 5, 2007. Revised December 5, 2007. Accepted December 6, 2007.
To understand how potential for G-quadruplex formation might influence regulation of gene expression, we examined the 2 kb spanning the transcription start sites (TSS) of the 18 217 human RefSeq genes, distinguishing contributions of template and nontemplate strands. Regions both upstream and downstream of the TSS are G-rich, but the downstream region displays a clear bias toward G-richness on the nontemplate strand. Upstream of the TSS, much of the G-richness and potential for G-quadruplex formation derives from the presence of well-defined canonical regulatory motifs in duplex DNA, including CpG dinucleotides which are sites of regulatory methylation, and motifs recognized by the transcription factor SP1. This challenges the notion that quadruplex formation upstream of the TSS contributes to regulation of gene expression. Downstream of the TSS, G-richness is concentrated in the first intron, and on the nontemplate strand, where polymorphic sequence elements with potential to form G-quadruplex structures and which cannot be accounted for by known regulatory motifs are found in almost 3000 (16%) of the human RefSeq genes, and are conserved through frogs. These elements could in principle be recognized either as DNA or as RNA, providing structural targets for regulation at the level of transcription or RNA processing.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Du, Y. Zhao, and N. Li Genome-wide colonization of gene regulatory elements by G4 DNA motifs Nucleic Acids Res., November 1, 2009; 37(20): 6784 - 6798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-w. Zheng, Z. Chen, Y.-h. Hao, and Z. Tan Molecular crowding creates an essential environment for the formation of stable G-quadruplexes in long double-stranded DNA Nucleic Acids Res., October 25, 2009; (2009) gkp898v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Creacy, E. D. Routh, F. Iwamoto, Y. Nagamine, S. A. Akman, and J. P. Vaughn G4 Resolvase 1 Binds Both DNA and RNA Tetramolecular Quadruplex with High Affinity and Is the Major Source of Tetramolecular Quadruplex G4-DNA and G4-RNA Resolving Activity in HeLa Cell Lysates J. Biol. Chem., December 12, 2008; 283(50): 34626 - 34634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Huppert, A. Bugaut, S. Kumari, and S. Balasubramanian G-quadruplexes: the beginning and end of UTRs Nucleic Acids Res., November 1, 2008; 36(19): 6260 - 6268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Paramasivan and P. H. Bolton Mix and measure fluorescence screening for selective quadruplex binders Nucleic Acids Res., October 1, 2008; 36(17): e106 - e106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kumar and S. Maiti A thermodynamic overview of naturally occurring intramolecular DNA quadruplexes Nucleic Acids Res., October 1, 2008; 36(17): 5610 - 5622. [Abstract] [Full Text] [PDF]
|
|