Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10.
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.
Menheniott
Trevelyan R
TR
King's College London, Department of Medical and Molecular Genetics, 8th Floor Guy's Tower, London SE1 9RT, England.
Woodfine
Kathryn
K
Schulz
Reiner
R
Wood
Andrew J
AJ
Monk
David
D
Giraud
Andrew S
AS
Baldwin
H Scott
HS
Moore
Gudrun E
GE
Oakey
Rebecca J
RJ
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004296:Dopa Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D051383:GRB10 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics / Q000378:metabolism
C096541:Cobl protein, mouse; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011506:Proteins; D051383:GRB10 Adaptor Protein; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C522287:FIGNL1 protein, mouse; D004296:Dopa Decarboxylase