1. Tissue-specific and imprinted epigenetic modifications of the human NDN gene.
- Author
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Lau JC, Hanel ML, and Wevrick R
- Subjects
- Acetylation, Alleles, Autoantigens, Cell Line, Cells, Cultured, CpG Islands, DNA Methylation, Female, Histones chemistry, Histones metabolism, Humans, Lysine metabolism, Organ Specificity, Ribonucleoproteins, Small Nuclear genetics, snRNP Core Proteins, Epigenesis, Genetic, Genomic Imprinting, Nerve Tissue Proteins genetics, Nuclear Proteins genetics
- Abstract
Allele-specific DNA methylation, histone acetylation and histone methylation are recognized as epigenetic characteristics of imprinted genes and imprinting centers (ICs). These epigenetic modifications are also used to regulate tissue-specific gene expression. Epigenetic differences between alleles can be significant either in the function of the IC or in the cis-acting effect of the IC on 'target' genes responding to it. We have now examined the epigenetic characteristics of NDN, a target gene of the chromosome 15q11-q13 Prader-Willi Syndrome IC, using sodium bisulfite sequencing to analyze DNA methylation and chromatin immunoprecipitation to analyze histone modifications. We observed a bias towards maternal allele-specific DNA hypermethylation of the promoter CpG island of NDN, independent of tissue-specific transcriptional activity. We also found that NDN lies in a domain of paternal allele-specific histone hyperacetylation that correlates with transcriptional state, and a domain of differential histone H3 lysine 4 di- and tri-methylation that persists independent of transcription. These results suggest that DNA methylation and histone H3 lysine 4 methylation are persistent markers of imprinted gene regulation while histone acetylation participates in tissue-specific activity and silencing in somatic cells.
- Published
- 2004
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