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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATPases Associated with Diverse Cellular Activities
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Alleles*
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Animals
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Base Sequence
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Cytoskeletal Proteins
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DNA (Cytosine-5-)-Methyltransferases / genetics
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DNA (Cytosine-5-)-Methyltransferases / metabolism
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DNA Methylation
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Dopa Decarboxylase / genetics*
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Dopa Decarboxylase / metabolism*
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Exons / genetics*
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GRB10 Adaptor Protein / genetics
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GRB10 Adaptor Protein / metabolism*
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Genomic Imprinting / genetics*
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Humans
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Mice
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Mice, Transgenic
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Microfilament Proteins
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Microtubule-Associated Proteins
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Myocardium / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Organ Specificity
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Proteins / genetics
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Proteins / metabolism
Substances
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Cobl protein, mouse
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Cytoskeletal Proteins
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Microfilament Proteins
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Microtubule-Associated Proteins
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Nuclear Proteins
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Proteins
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GRB10 Adaptor Protein
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Dnmt3l protein, mouse
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DNA (Cytosine-5-)-Methyltransferases
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Adenosine Triphosphatases
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ATPases Associated with Diverse Cellular Activities
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FIGNL1 protein, mouse
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Dopa Decarboxylase