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Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10

Research output: Contribution to journalArticle

  • Trevelyan R. Menheniott
  • Kathryn Woodfine
  • Reiner Schulz
  • Andrew J. Wood
  • David Monk
  • Andrew S. Giraud
  • H. Scott Baldwin
  • Gudrun E. Moore
  • Rebecca J. Oakey

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)386-396
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2008

Abstract

By combining a tissue-specific microarray screen with mouse uniparental duplications, we have identified a novel imprinted gene, Dopa decarboxylase (Ddc), on chromosome 11. Ddc_exon1a is a 2-kb transcript variant that initiates from an alternative first exon in intron 1 of the canonical Ddc transcript and is paternally expressed in trabecular cardiomyocytes of the embryonic and neonatal heart. Ddc displays tight conserved linkage with the maternally expressed and methylated Grb10 gene, suggesting that these reciprocally imprinted genes may be coordinately regulated. In Dnmt3L mutant embryos that lack maternal germ line methylation imprints, we show that Ddc is overexpressed and Grb10 is silenced. Their imprinting is therefore dependent on maternal germ line methylation, but the mechanism at Ddc does not appear to involve differential methylation of the Ddc exon1a promoter region and may instead be provided by the oocyte mark at Grb10. Our analysis of Ddc redefines the imprinted Grb10 domain on mouse proximal chromosome 11 and identifies Ddc_exon1a as the first example of a heart-specific imprinted gene.

    Research areas

  • AMINO-ACID DECARBOXYLASE, SILVER-RUSSELL-SYNDROME, TISSUE-SPECIFIC EXPRESSION, BIPOLAR AFFECTIVE-DISORDER, DIFFERENTIAL METHYLATION, NEURONAL PROMOTER, TYROSINE-HYDROXYLASE, BIRTH-WEIGHT, MOUSE GRB10, IGF2 GENE

ID: 14468241