@article{b6c74f31f43741f38ff6fbe3646d1531,
title = "Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors",
abstract = "Epigenetic control of transcription is essential for mammalian development and its deregulation causes human disease. For example, loss of proper imprinting control at the IGF2-H19 domain is a hallmark of cancer and Beckwith-Wiedemann syndrome, with no targeted therapeutic approaches available. To address this deficiency, we engineered zinc-finger transcription proteins (ZFPs) that specifically activate or repress the IGF2 and H19 genes in a domain-dependent manner. Importantly, we used these ZFPs successfully to reactivate the transcriptionally silent IGF2 and H19 alleles, thus overriding the natural mechanism of imprinting and validating an entirely novel avenue for 'transcription therapy' of human disease.",
keywords = "Gene regulation, Imprinting, Transcriptional repression, Zinc-finger proteins",
author = "Y. Jouvenot and V. Ginjala and L. Zhang and Liu, {P. Q.} and M. Oshimura and Feinberg, {A. P.} and Wolffe, {A. P.} and Rolf Ohlsson and Gregory, {P. D.}",
note = "Funding Information: We thank Andrew Jamieson, Edward Rebar and Qiang Liu for the design and selections of the ZFPs in the library, Monica Miller and Matthew Mendel for assembly and initial testing of the ZFP constructs, Xiaohong Zhong for technical help in the generation of the stable cell line, and Fyodor Urnov for comments on the manuscript. We are also grateful to Edward Lanphier, Casey Case, Carl Pabo and Elizabeth Wolffe for encouragement and support. This work was supported in part by grants from the Swedish Science Research Council (VR), the Swedish Cancer Research Foundation (CF), the Swedish Pediatric Cancer Foundation (BCF) and the Lundberg Foundation all to RO, and NIH grant CA54358 to APF. We dedicate this work to the memory of our friend, colleague and mentor Alan P Wolffe. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",
year = "2003",
month = mar,
doi = "10.1038/sj.gt.3301930",
language = "English (US)",
volume = "10",
pages = "513--522",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "6",
}