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Human Molecular Genetics, 2002, Vol. 11, No. 1 77-86
© 2002 Oxford University Press

Epigenetic analysis of the Dlk1–Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2–H19

Shuji Takada, Martina Paulsen, Maxine Tevendale, Chen-En Tsai, Gavin Kelsey1, Bruce M. Cattanach2 and Anne C. Ferguson-Smith+

Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK, 1Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK and 2MRC Mammalian Genetics Unit, Didcot, Oxon, UK

Dlk1 and Gtl2 are reciprocally imprinted genes located 80 kb apart on mouse chromosome 12. Similarities between this domain and that of the well characterized Igf2–H19 locus have been previously noted. Comparative genomic and epigenetic analysis of these two domains might help identify allele-specific epigenetic regulatory elements and common features involved in aspects of imprinting control. Here we describe a detailed methylation analysis of the Dlk1–Gtl2 domain on both parental alleles in the mouse. Like the Igf2–H19 domain, areas of differential methylation are hypermethylated on the paternal allele and hypomethylated on the maternal allele. Three differentially methylated regions (DMRs), each with different epigenetic characteristics, have been identified. One DMR is intergenic, contains tandem repeats and is the only region that inherits a paternal methylation mark from the germline. An intronic DMR contains a conserved putative CTCF-binding domain. All three DMRs have both unique and common features compared to those identified in the Igf2–H19 domain.

+ To whom correspondence should be addressed. Tel: +44 1223 333 750; Fax: +44 1223 333 786; Email: afsmith@mole.bio.cam.ac.uk Present address: Martina Paulsen, FR 8.2 Genetik, Gebäude 6, Universität des Saarlandes, Postfach 151150, D-66041 Saarbrücken, Germany


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