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Expression of delta-like 1 homologue and insulin-like growth factor 2 through epigenetic regulation of the genes during development of mouse molar.

Abstract

Delta-like 1 homolog (Dlk1) and insulin-like growth factor 2 (Igf2) are two of six well-studied mouse imprinted gene clusters that are paternally expressed. Their expression is also linked to their maternally expressed non-coding RNAs, encoded by Gene trap locus 2 (Gtl2) and Imprinted maternally expressed transcript (H19), co-located as imprinted gene clusters. Using deoxyoligonucleotide microarrays and real-time RT-PCR analysis we showed Dlk1 and Gtl2 to exhibit a time-course of expression during tooth development that was similar to that of Igf2 and H19. Western blot analysis of proteins encoded by Dlk1 and Igf2 suggested that the levels of these proteins reflected those of the corresponding mRNAs. Immunohistochemical studies of DLK1 in murine molars detected the protein in both epithelial and mesenchymal regions, in developing cusp mesenchyme, and in newly synthesized enamel and dentin tubules. IGF2 protein was detected primarily at prenatal stages, suggesting that it may be active before birth. Analysis of methylation of cytosine-phosphate-guanine (CpG) islands in both Dlk1 and Igf2 suggested the presence of an increasing fraction of hypermethylated bases with increasing time of development. The increased levels of hypermethylation coincided both with the diminished levels of expression of Dlk1 and Igf2 and with decreased levels of DLK1 and IGF2 proteins in the tooth germ, suggesting that their expression is regulated via methylation of CpG islands present in these genes.

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  • Publisher Full Text

    • Authors

    Khan QE, Sehic A, Skalleberg N, Landin MA, Khuu C, Risnes S, Osmundsen H

    Institution

    Department of Oral Biology, University of Oslo, Oslo, Norway.

    Source

    European journal of oral sciences 120:4 2012 Aug pg 292-302

    MeSH

    Analysis of Variance
    Animals
    DNA Methylation
    Epigenomics
    Gene Expression Regulation, Developmental
    Genomic Imprinting
    Insulin-Like Growth Factor II
    Intercellular Signaling Peptides and Proteins
    Mice
    Mice, Inbred BALB C
    Multigene Family
    Odontogenesis
    Reverse Transcriptase Polymerase Chain Reaction
    Tissue Array Analysis
    Tooth Germ

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22813219