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Scientific article
English

Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes

Published inMolecular and Cellular Biology, vol. 26, no. 22, p. 8347-8356
Publication date2006
Abstract

Landmark features of imprinted genes are differentially methylated domains (DMDs), in which one parental allele is methylated on CpG dinucleotides and the opposite allele is unmethylated. Genetic experiments in the mouse have shown that DMDs are required for the parent-specific expression of linked clusters of imprinted genes. To understand the mechanism whereby the differential methylation is established and maintained, we analyzed a series of transgenes containing DMD sequences and showed that imperfect tandem repeats from DMDs associated with the Snurf/Snrpn, Kcnq1, and Igf2r gene clusters govern transgene imprinting. For the Igf2r DMD the minimal imprinting signal is two unit copies of the tandem repeat. This imprinted transgene behaves identically to endogenous imprinted genes in Dnmt1o and Dnmt3L mutant mouse backgrounds. The primary function of the imprinting signal within the transgene DMD is to maintain, during embryogenesis and a critical period of genomic reprogramming, parent-specific DNA methylation states established in the germ line. This work advances our understanding of the imprinting mechanism by defining a genomic signal that dependably perpetuates an epigenetic state during postzygotic development.

Keywords
  • Animals
  • CpG Islands
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases/genetics
  • DNA Methylation
  • Gene Expression Regulation
  • Genes
  • Immunoglobulin
  • Genes
  • Myc
  • Genomic Imprinting
  • Mice
  • Mice
  • Transgenic
  • Models
  • Genetic
  • Nuclear Proteins/genetics
  • Receptor
  • IGF Type 2/genetics
  • Tandem Repeat Sequences
Affiliation Not a UNIGE publication
Citation (ISO format)
REINHART, Bonnie, GIACOBINO, Ariane, CHAILLET, J Richard. Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes. In: Molecular and Cellular Biology, 2006, vol. 26, n° 22, p. 8347–8356. doi: 10.1128/MCB.00981-06
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0270-7306
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