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Molecular and Cellular Biology, January 2008, p. 386-396, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.00862-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genomic Imprinting of Dopa decarboxylase in Heart and Reciprocal Allelic Expression with Neighboring Grb10

Trevelyan R. Menheniott,^1, Kathryn Woodfine,¹ Reiner Schulz,¹ Andrew J. Wood,¹ David Monk,² Andrew S. Giraud,⁴ H. Scott Baldwin,³ Gudrun E. Moore,² and Rebecca J. Oakey^1*

King's College London, Department of Medical and Molecular Genetics, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, United Kingdom,¹ Institute of Child Health, Clinical and Molecular Genetics, University College London, 30 Guildford Street, London WC1N 1EH, United Kingdom,² Department of Pediatrics, Vanderbilt University Medical Center, B3301 MCN, Nashville, Tennessee,³ Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia⁴

Received 16 May 2007/ Returned for modification 14 June 2007/ Accepted 8 October 2007

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.

Published ahead of print on 29 October 2007.

Present address: Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.