Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors

Y. Jouvenot, V. Ginjala, L. Zhang, P. Q. Liu, M. Oshimura, A. P. Feinberg, A. P. Wolffe, Rolf Ohlsson, P. D. Gregory

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalGene Therapy
Volume10
Issue number6
DOIs
StatePublished - Mar 2003

Keywords

  • Gene regulation
  • Imprinting
  • Transcriptional repression
  • Zinc-finger proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors'. Together they form a unique fingerprint.

Cite this