Inhibition of methylation and changes in gene expression in relation to neural tube defects

I.J. van der Linden, S.G. Heil, M. van Egmont-Petersen, H.W. Straaten, M. den Heijer

    Research output: Contribution to journalArticleAcademicpeer-review

    19 Citations (Scopus)

    Abstract

    BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that inhibition of methylation by Adox in our in vitro chick embryo model will affect the expression of genes that may be involved in neurulation. In the present study, we therefore examined differential gene expression between Adox-treated and control chick embryos, using the Affymetrix Genechip Chicken Genome Array. METHODS: Chick embryos of 4/5 somites were cultured in vitro with saline (control) or Adox and cranial parts were excised. Gene expression profiling was determined using the Affymetrix Genechip Chicken Genome Array on RNA isolated from two pools of Adox-treated cranial parts (n = 12) and two pools of saline-treated cranial parts (n = 12). Microarray data were validated by QPCR analysis. RESULTS: In the Adox-treated chick embryos, 45 probesets were up-regulated (fold 2.0, p <0.05) and 32 probesets were down-regulated (fold 0.5, p <0.05). Of the 15 genes selected for QPCR analysis, the up-regulation of phosphoserine phosphatase (PSPH), unc-51-like kinase 1 (ULK1), and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor 1 (CXCL12/SDF-1) was confirmed. CONCLUSIONS: Inhibition of methylation by Adox affects gene expression in our in vitro chick embryo model. Further research will focus on the gene-specific methylation patterns of PSPH, ULK1, and CXCL12/SDF-1 and the role of the products of these genes in neurulation.
    Original languageEnglish
    Pages (from-to)676-683
    JournalBirth defects research. Part A, Clinical and molecular teratology
    Volume82
    Issue number10
    DOIs
    Publication statusPublished - 2008

    Keywords

    • factor-i
    • methylenetetrahydrofolate reductase
    • serine/threonine kinase
    • caenorhabditis-elegans
    • mammalian development
    • common mutation
    • risk-factor
    • dna
    • serine
    • folate

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