Nucleic Acids Research Advance Access originally published online on December 14, 2006
Nucleic Acids Research 2007 35(2):406-413; doi:10.1093/nar/gkl1057
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 2 406-413
© 2006 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 |
G-quadruplexes in promoters throughout the human genome
1 Cambridge University Chemical Laboratory, University of Cambridge Lensfield Road, Cambridge CB2 1EW, UK 2 Wellcome Trust Sanger Institute, Hinxton Cambridge CB10 1SA, UK
*To whom correspondence should be addressed. Tel: +44 1223 336447; Fax: +44 1223 336913; Email: sb10031{at}cam.ac.uk
Received October 18, 2006. Revised November 17, 2006. Accepted November 18, 2006.
Certain G-rich DNA sequences readily form four-stranded structures called G-quadruplexes. These sequence motifs are located in telomeres as a repeated unit, and elsewhere in the genome, where their function is currently unknown. It has been proposed that G-quadruplexes may be directly involved in gene regulation at the level of transcription. In support of this hypothesis, we show that the promoter regions (1 kb upstream of the transcription start site TSS) of genes are significantly enriched in quadruplex motifs relative to the rest of the genome, with >40% of human gene promoters containing one or more quadruplex motif. Furthermore, these promoter quadruplexes strongly associate with nuclease hypersensitive sites identified throughout the genome via biochemical measurement. Regions of the human genome that are both nuclease hypersensitive and within promoters show a remarkable (230-fold) enrichment of quadruplex elements, compared to the rest of the genome. These quadruplex motifs identified in promoter regions also show an interesting structural bias towards more stable forms. These observations support the proposal that promoter G-quadruplexes are directly involved in the regulation of gene expression.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Shen, L. Gao, M. Balakrishnan, and R. A. Bambara A Recombination Hot Spot in HIV-1 Contains Guanosine Runs That Can Form a G-quartet Structure and Promote Strand Transfer in Vitro J. Biol. Chem., December 4, 2009; 284(49): 33883 - 33893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Yang, J. Xiang, S. Yang, Q. Li, Q. Zhou, A. Guan, X. Zhang, H. Zhang, Y. Tang, and G. Xu Verification of specific G-quadruplex structure by using a novel cyanine dye supramolecular assembly: II. The binding characterization with specific intramolecular G-quadruplex and the recognizing mechanism Nucleic Acids Res., November 19, 2009; (2009) gkp1045v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Halder, M. Wieland, and J. S. Hartig Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes Nucleic Acids Res., November 1, 2009; 37(20): 6811 - 6817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fernando, S. Sewitz, J. Darot, S. Tavare, J. L. Huppert, and S. Balasubramanian Genome-wide analysis of a G-quadruplex-specific single-chain antibody that regulates gene expression Nucleic Acids Res., November 1, 2009; 37(20): 6716 - 6722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. I. Onyshchenko, T. I. Gaynutdinov, E. A. Englund, D. H. Appella, R. D. Neumann, and I. G. Panyutin Stabilization of G-quadruplex in the BCL2 promoter region in double-stranded DNA by invading short PNAs Nucleic Acids Res., October 9, 2009; (2009) gkp840v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Neaves, J. L. Huppert, R. M. Henderson, and J. M. Edwardson Direct visualization of G-quadruplexes in DNA using atomic force microscopy Nucleic Acids Res., October 1, 2009; 37(18): 6269 - 6275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nakken, T. Rognes, and E. Hovig The disruptive positions in human G-quadruplex motifs are less polymorphic and more conserved than their neutral counterparts Nucleic Acids Res., September 1, 2009; 37(17): 5749 - 5756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gonzalez, K. Guo, L. Hurley, and D. Sun Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein J. Biol. Chem., August 28, 2009; 284(35): 23622 - 23635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Verma, V. K. Yadav, R. Basundra, A. Kumar, and S. Chowdhury Evidence of genome-wide G4 DNA-mediated gene expression in human cancer cells Nucleic Acids Res., July 13, 2009; (2009) gkn1076v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Stegle, L. Payet, J.-L. Mergny, D. J. C. MacKay, and J. L. Huppert Predicting and understanding the stability of G-quadruplexes Bioinformatics, June 15, 2009; 25(12): i374 - i1382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Schonhoft, R. Bajracharya, S. Dhakal, Z. Yu, H. Mao, and S. Basu Direct experimental evidence for quadruplex-quadruplex interaction within the human ILPR Nucleic Acids Res., June 1, 2009; 37(10): 3310 - 3320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Paramasivam, A. Membrino, S. Cogoi, H. Fukuda, H. Nakagama, and L. E. Xodo Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription Nucleic Acids Res., May 1, 2009; 37(9): 2841 - 2853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Siegel, D. R. Hekstra, L. E. Kemp, L. M. Figueiredo, J. E. Lowell, D. Fenyo, X. Wang, S. Dewell, and G. A.M. Cross Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei Genes & Dev., May 1, 2009; 23(9): 1063 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Thakur, P. Kumar, K. Halder, A. Verma, A. Kar, J.-L. Parent, R. Basundra, A. Kumar, and S. Chowdhury Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression Nucleic Acids Res., January 1, 2009; 37(1): 172 - 183. [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]
|
|
|
|
|
|
A. N. Lane, J. B. Chaires, R. D. Gray, and J. O. Trent Stability and kinetics of G-quadruplex structures Nucleic Acids Res., October 1, 2008; 36(17): 5482 - 5515. [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]
|
|
|
|
|
|
R. D. Gray and J. B. Chaires Kinetics and mechanism of K+- and Na+-induced folding of models of human telomeric DNA into G-quadruplex structures Nucleic Acids Res., July 1, 2008; 36(12): 4191 - 4203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cogoi, M. Paramasivam, B. Spolaore, and L. E. Xodo Structural polymorphism within a regulatory element of the human KRAS promoter: formation of G4-DNA recognized by nuclear proteins Nucleic Acids Res., June 1, 2008; 36(11): 3765 - 3780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sun, W.-J. Liu, K. Guo, J. J. Rusche, S. Ebbinghaus, V. Gokhale, and L. H. Hurley The proximal promoter region of the human vascular endothelial growth factor gene has a G-quadruplex structure that can be targeted by G-quadruplex-interactive agents Mol. Cancer Ther., April 1, 2008; 7(4): 880 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Eddy and N. Maizels Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes Nucleic Acids Res., March 27, 2008; 36(4): 1321 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Du, Y. Zhao, and N. Li Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription Genome Res., February 1, 2008; 18(2): 233 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Hershman, Q. Chen, J. Y. Lee, M. L. Kozak, P. Yue, L.-S. Wang, and F. B. Johnson Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae Nucleic Acids Res., January 17, 2008; 36(1): 144 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhang, Y. Lin, and C.-T. Zhang Greglist: a database listing potential G-quadruplex regulated genes Nucleic Acids Res., January 11, 2008; 36(suppl_1): D372 - D376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Yadav, J. K. Abraham, P. Mani, R. Kulshrestha, and S. Chowdhury QuadBase: genome-wide database of G4 DNA occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes Nucleic Acids Res., January 11, 2008; 36(suppl_1): D381 - D385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Huppert Four-stranded DNA: cancer, gene regulation and drug development Phil Trans R Soc A, December 15, 2007; 365(1861): 2969 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Patel, A. T. Phan, and V. Kuryavyi Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics Nucleic Acids Res., December 3, 2007; 35(22): 7429 - 7455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Todd, S. M. Haider, G. N. Parkinson, and S. Neidle Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter Nucleic Acids Res., September 27, 2007; 35(17): 5799 - 5808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Rachwal, I. S. Findlow, J. M. Werner, T. Brown, and K. R. Fox Intramolecular DNA quadruplexes with different arrangements of short and long loops Nucleic Acids Res., June 18, 2007; (2007) gkm316v1. [Abstract] [Full Text] [PDF]
|
|