Genome-wide analysis of a G-quadruplex-specific single-chain antibody that regulates gene expression.
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.
Fernando
Himesh
H
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Sewitz
Sven
S
Darot
Jeremy
J
Tavaré
Simon
S
Huppert
Julian Leon
JL
Balasubramanian
Shankar
S
D045744:Cell Line, Tumor; D004247:DNA / Q000276:immunology / Q000378:metabolism; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D057127:Single-Chain Antibodies; D004247:DNA