A silencer element identified in Drosophila is required for imprinting of H19 reporter transgenes in mice

Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9242-7. doi: 10.1073/pnas.96.16.9242.

Abstract

The H19 gene is subject to genomic imprinting because it is methylated and repressed after paternal inheritance and is unmethylated and expressed after maternal inheritance. We recently identified a 1.1-kb control element in the upstream region of the H19 gene that functions as a cis-acting silencer element in Drosophila. Here we investigate the function of this element in mice. We demonstrate that both H19-lacZ and H19-PLAP reporter transgenes can undergo imprinting with repression and hypermethylation after paternal transmission at many integration sites. However, transgenes that were deleted for the 1.1-kb silencer element showed loss of paternal repression, but they did not show marked changes in the paternal methylation of the remaining upstream region. This study demonstrates that the 1.1-kb control element identified in Drosophila is required to silence paternally transmitted H19 minitransgenes in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics*
  • Animals
  • Chromosome Mapping
  • DNA Methylation
  • Drosophila / genetics*
  • Female
  • Gene Library
  • Genes, Reporter
  • Genes, Tumor Suppressor*
  • Genetic Techniques
  • Genomic Imprinting*
  • Isoenzymes / genetics*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Muscle Proteins / genetics*
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Testis / enzymology
  • beta-Galactosidase / genetics

Substances

  • H19 long non-coding RNA
  • Isoenzymes
  • Muscle Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • germ-cell AP isoenzyme
  • Alkaline Phosphatase
  • beta-Galactosidase