Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12.
Genomic imprinting causes parental origin-specific gene expression. 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 gametogenesis. 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 snoRNAs. 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.
Lin
Shau-Ping
SP
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Youngson
Neil
N
Takada
Shuji
S
Seitz
Hervé
H
Reik
Wolf
W
Paulsen
Martina
M
Cavaille
Jerome
J
Ferguson-Smith
Anne C
AC
D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes; D002883:Chromosomes, Human, Pair 14; D019175:DNA Methylation; D004622:Embryo, Mammalian; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D040582:Inheritance Patterns; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D005810:Multigene Family; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding
D047908:Intracellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; C422882:MEG3 non-coding RNA, mouse; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; C064045:delta protein