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Nucleic Acids Research Advance Access published online on September 10, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp740
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© 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.

Gene Regulation, Chromatin and Epigenetics

Genome-wide analysis of a G-quadruplex-specific single-chain antibody that regulates gene expression

Himesh Fernando1, Sven Sewitz1, Jeremy Darot2, Simon Tavaré2, Julian Leon Huppert3 and Shankar Balasubramanian1,4,*

1Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, 2CRUK Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, 3Cavendish Laboratory, Cambridge CB3 0HE and 4School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK

*To whom correspondence should be addressed. Tel: +44 1223 336347; Fax: +44 1223 336913; Email: sb10031{at}cam.ac.uk

Received July 17, 2009. Revised August 20, 2009. Accepted August 22, 2009.

G-quadruplex nucleic acids have been proposed to play a role in a number of fundamental biological processes that include transcription and translation. We have developed a single-chain antibody that is selective for G-quadruplex DNA over double-stranded DNA, and here show that when it is expressed in human cells, it significantly affects the expression of a wide variety of genes, in a manner that correlates with the presence of predicted G-quadruplexes. We observe cases where gene expression is increased or decreased, and that there are apparent interactions with G-quadruplex motifs at the beginning and end of the genes, and on either strand. The outcomes of this genome-wide study demonstrate that G-quadruplex recognition by the antibody has physiological consequences, and provides insights into some of the complexity associated with G-quadruplex-based regulation.

Correspondence may also be addressed to Julian Leon Huppert. Tel: +44 1223 337256; Fax: +44 1223 337000; E-mail: jlh29{at}cam.ac.uk.

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


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