Restricted co-expression of Dlk1 and the reciprocally imprinted non-coding RNA, Gtl2: Implications for cis-acting control
Dlk1 and Gtl2 are reciprocally imprinted neighboring genes located within a 1 Mb imprinted domain on murine distal chromosome 12. The two genes are expressed and developmentally regulated during mammalian embryogenesis. Dlk1/Pref1 encodes a transmembrane protein with homology to members of the Notch...
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Published in | Developmental biology Vol. 306; no. 2; pp. 810 - 823 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.06.2007
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Subjects | |
Online Access | Get full text |
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Summary: | Dlk1 and
Gtl2 are reciprocally imprinted neighboring genes located within a 1 Mb imprinted domain on murine distal chromosome 12. The two genes are expressed and developmentally regulated during mammalian embryogenesis.
Dlk1/Pref1 encodes a transmembrane protein with homology to members of the
Notch/Delta developmental signaling pathway and
Gtl2 generates alternatively spliced poly-adenylated transcripts lacking a conserved open reading frame. An intergenic differentially methylated region (IG-DMR) located 13 kb upstream of
Gtl2 has been shown to regulate imprinting throughout the domain by an as yet unknown mechanism. In order to gain insights into regulation at this domain and to compare it with imprinting control at other loci, we compared the expression profile of
Dlk1 with
Gtl2 during mouse embryogenesis in normal conceptuses and in those with uniparental disomy for chromosome 12. The expression profile of these genes suggests a causative role for
Dlk1 and
Gtl2 in the pathologies found in uniparental disomy animals, characterized by defects in skeletal muscle maturation, bone formation, placenta size and organization and prenatal lethality. Here, we show restricted overlap in cellular expression of these two genes throughout development.
Dlk1 is imprinted and expressed in cell types within the lung, liver and placenta where
Gtl2 is not expressed.
Gtl2 is highly expressed in the central nervous system (CNS), whereas
Dlk1 is found localized to specific regions such as the hypothalamus. Co-expression is observed in most of the mesodermal-derived tissues, notably the skeletal muscle where both genes are strongly co-expressed. In this tissue,
Dlk1 shows a relaxation of imprinting with some expression from the maternal allele. These findings indicate that the general mechanism of imprinting at the stages analyzed is not through the co-ordinate non-coding RNA or insulator mechanisms observed for other imprinted domains, and suggest that the two genes have independent tissue-specific functions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1606 1095-564X |
DOI: | 10.1016/j.ydbio.2007.02.043 |