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A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation

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  • Andrew J. Wood
  • Roland G. Roberts
  • David Monk
  • Gudrun E. Moore
  • Reiner Schulz
  • Rebecca J. Oakey

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    Rights statement: © 2007 Wood et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Original languageEnglish
Article numbere20
Number of pages12
JournalPLoS Genetics
Volume3
Issue number2
DOIs
Publication statusPublished - Feb 2007

Abstract

Imprinted genes undergo epigenetic modifications during gametogenesis, which lead to transcriptional silencing of either the maternally or the paternally derived allele in the subsequent generation. Previous work has suggested an association between imprinting and the products of retrotransposition, but the nature of this link is not well defined. In the mouse, three imprinted genes have been described that originated by retrotransposition and overlap CpG islands which undergo methylation during oogenesis. Nap1l5, U2af1-rs1, and Inpp5f_v2 are likely to encode proteins and share two additional genetic properties: they are located within introns of host transcripts and are derived from parental genes on the X chromosome. Using these sequence features alone, we identified Mcts2, a novel candidate imprinted retrogene on mouse Chromosome 2. Mcts2 has been validated as imprinted by demonstrating that it is paternally expressed and undergoes promoter methylation during oogenesis. The orthologous human retrogenes NAP1L5, INPP5F_V2, and MCTS2 are also shown to be paternally expressed, thus delineating novel imprinted loci on human Chromosomes 4, 10, and 20. The striking correlation between imprinting and X chromosome provenance suggests that retrotransposed elements with homology to the X chromosome can be selectively targeted for methylation during mammalian oogenesis.

    Research areas

  • TRANSPOSABLE ELEMENTS, HUMAN GENOME, HISTOCOMPATIBILITY ANTIGEN, CYTOSINE METHYLATION, CANDIDATE ONCOGENE, TANDEM REPEATS, MOUSE MURR1, CPG ISLAND, IDENTIFICATION, EVOLUTION

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