Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

Nat Biotechnol. 1999 Mar;17(3):241-5. doi: 10.1038/6981.

Abstract

Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / genetics
  • Animals
  • Blotting, Northern
  • Cells, Cultured
  • Chickens / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression
  • Gene Library
  • Genetic Therapy*
  • Growth Hormone-Releasing Hormone / metabolism
  • HeLa Cells
  • Humans
  • Luciferases / metabolism
  • MEF2 Transcription Factors
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Models, Biological
  • Muscle, Skeletal / metabolism*
  • Myogenic Regulatory Factors
  • Myosin Light Chains / genetics
  • Nuclear Proteins / genetics
  • Promoter Regions, Genetic*
  • Radioimmunoassay
  • Serum Response Factor
  • Time Factors
  • Tissue Distribution
  • Transcription Factors / genetics*
  • beta-Galactosidase / metabolism

Substances

  • Actins
  • DNA-Binding Proteins
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Myosin Light Chains
  • Nuclear Proteins
  • Serum Response Factor
  • Transcription Factors
  • Growth Hormone-Releasing Hormone
  • Luciferases
  • beta-Galactosidase