Imprinting and gene silencing in mice and Drosophila.
H19 and Igf2 are located within a large imprinting domain that confers monoallelic silencing of parental alleles. The silent paternal allele of H19 is hypermethylated and relatively resistant to nucleases. Using a 130 kb yeast artificial chromosome clone, appropriate imprinting of both H19 and Igf2 was observed at single insert loci in transgenic mice. Imprinting was also observed for H19-lacZ transgenes containing 4 kb of upstream sequence, but only at multicopy loci. The H19 RNA is therefore not essential for imprinting. When the H19-lacZ transgene was introduced into Drosophila, a 1.2 kb region was identified within the 4 kb upstream flank that functioned as a bi-directional silencer. This cis element is located within a region that is apparently necessary for imprinting in mice. These studies suggest an evolutionarily conserved mechanism for gene silencing in Drosophila and imprinting in mice. We propose a new model for imprinting of H19 and Igf2 in mice in which silencing of H19 is the default state, and activation of the maternal allele requires a specific activator element.
Brenton
J D
JD
Wellcome/CRC Institute of Cancer and Developmental Biology, University of Cambridge, UK.
Ainscough
J F
JF
Lyko
F
F
Paro
R
R
Surani
M A
MA
D000818:Animals; D002875:Chromosomes; D018244:Chromosomes, Artificial, Yeast; D004330:Drosophila / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II