Nature Genetics35, 97 - 102 (2003)
Published online: 24 August 2003; | doi:10.1038/ng1233
Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12
Shau-Ping Lin1, Neil Youngson1, Shuji Takada1, 4, Hervé Seitz2, Wolf Reik3, Martina Paulsen1, 4, Jerome Cavaille2
& Anne C Ferguson-Smith1
1
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
2
LBME-CNRS (UMR5099), Université P. Sabatier, 118 Route de Narbonne, 31062 Toulouse Cedex, France.
3
Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK.
4
Present addresses: Institute for Molecular Bioscience, The University of Queensland, Brisbane Qld 4072, Australia (S.T.); Universität des Saarlandes, FR Genetik, Postfach 151150, D-66041 Saarbrücken, Germany (M.P.).
Genomic imprinting causes parental origin−specific gene expression1. Cis-acting regulatory elements that control imprinting are not fully understood but involve regions that become differentially methylated on the two parental chromosomes during male and female gametogenesis2,
3,
4. Understanding properties of maternally and paternally inherited imprints provides insight into the mechanisms and evolution of genomic imprinting. Previously we identified an intergenic germline-derived differentially methylated region (IG-DMR) that is a candidate control element for an imprinted domain on distal mouse chromosome 12 (ref. 5). The 1-Mb cluster contains the paternally expressed protein-coding genes Dlk1 (refs. 6,7) and Dio3 (ref. 8,9) and several maternally expressed non-coding RNAs, including Gtl2 (refs. 6,7,10) and C/D snoRNAs11. A retrotransposon-like gene (Rtl1) is expressed from the paternal chromosome and has an antisense transcript expressed from the maternal chromosome containing two microRNAs with full complementarity to Rtl1 (ref. 12). Here we show that deletion of the IG-DMR from the maternally inherited chromosome causes bidirectional loss of imprinting of all genes in the cluster. When the deletion is transmitted from the father, imprinting is unaltered. These results prove that the IG-DMR is a control element for all imprinted genes on the maternal chromosome only and indicate that the two parental chromosomes control allele-specific gene expression differently.
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