Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region.
The Dlk1-Gtl2 domain on mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced this conserved region in the mouse and sheep and included the human sequence in a three species comparison. This analysis resulted in a precise conservation map and identification of highly conserved sequence elements, some of which we have shown previously to be differentially methylated in the mouse. Additionally, this analysis facilitated identification of a CpG-rich tandem repeat array located approximately 13-15 kb upstream of Gtl2. Furthermore, we have identified a third imprinted transcript that overlaps with the last Dlk1 exon in the mouse. This transcript lacks a conserved open reading frame and is probably generated by cleavage of extended Dlk1 transcripts. Because Dlk1 and Gtl2 share many of the imprinting properties of the well-characterized Igf2-H19 domain, it has been proposed that the two regions may be regulated in the same way. Comparative genomic examination of the two domains indicates that although there are similarities, other features are very different, including the location of conserved CTCF-binding sites, and the level of conservation at regulatory regions.
Paulsen
M
M
University of Cambridge, Department of Anatomy, Cambridge CB2 3DY, United Kingdom.
Takada
S
S
Youngson
N A
NA
Benchaib
M
M
Charlier
C
C
Segers
K
K
Georges
M
M
Ferguson-Smith
A C
AC
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005819:Genetic Markers / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D012756:Sheep; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C420116:Ihit1 protein, mouse; 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; D012097:Repressor Proteins; D014157:Transcription Factors; C064045:delta protein