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Related Experiment Videos

Repeat-induced gene silencing in mammals

D Garrick1, S Fiering, D I Martin

  • 1Department of Biochemistry, University of Sydney, New South Wales, Australia.

Nature Genetics
|January 13, 1998
PubMed
Summary

Gene silencing in transgenic mammals is influenced by transgene copy number. Reducing transgene copies in arrays significantly increases expression and reduces chromatin compaction and methylation.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Repeat-induced gene silencing (RGS) is observed in plants and Drosophila, where concatameric transgene arrays reduce expression.
  • In transgenic mammals, copy number effects on transgene expression are confounded by position effects.
  • Previous studies suggest a repressive influence of transgene copy number on expression in mammals.

Purpose of the Study:

  • To investigate the sole effect of transgene copy number on gene expression in mammals.
  • To eliminate position effects when analyzing copy number influence on transgene silencing.
  • To establish a transgenic mouse model for studying copy number-dependent gene regulation.

Main Methods:

  • Utilized the lox/Cre site-specific recombination system to generate transgenic mouse lines.
  • Created lines with varying numbers of transgenes integrated at the same chromosomal location.
  • Analyzed transgene expression levels, chromatin compaction, and DNA methylation.

Main Results:

  • Reduced transgene copy number led to a marked increase in transgene expression.
  • Decreased chromatin compaction was observed with lower transgene copy numbers.
  • Reduced DNA methylation at the transgene locus accompanied increased expression.
  • Established that multiple homologous transgene copies in concatameric arrays repress gene expression.

Conclusions:

  • Transgene copy number, independent of integration site, significantly impacts gene expression in mammals.
  • High transgene copy numbers in concatameric arrays induce gene silencing via epigenetic modifications.
  • The findings provide a clearer understanding of transgene silencing mechanisms in mammalian systems.

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