Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation

Agata Desantis, Annalisa Onori, Maria Grazia Di Certo, Elisabetta Mattei, Maurizio Fanciulli, Claudio Passananti, Nicoletta Corbi

Research output: Contribution to journalArticle

Abstract

Our aim is to upregulate the expression level of the dystrophin related gene utrophin in Duchenne muscular dystrophy, thus complementing the lack of dystrophin functions. To this end, we have engineered synthetic zinc finger based transcription factors. We have previously shown that the artificial three-zinc finger protein named Jazz fused with the Vp16 activation domain, is able to bind utrophin promoter A and to increase the endogenous level of utrophin in transgenic mice. Here, we report on an innovative artificial protein, named CJ7, that consists of Jazz DNA binding domain fused to a novel activation domain derived from the regulatory multivalent adaptor protein Che-1/AATF. This transcriptional activation domain is 100 amino acids in size and it is very powerful as compared to the Vp16 activation domain. We show that CJ7 protein efficiently promotes transcription and accumulation of the acetylated form of histone H3 on the genomic utrophin promoter locus.

Original languageEnglish
Pages (from-to)158-162
Number of pages5
JournalNeuromuscular Disorders
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • Activation domain
  • Artificial transcription factor
  • Che-1/AATF
  • DMD
  • Dystrophin
  • Utrophin
  • Zinc finger

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

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