Tissue-specific and imprinted epigenetic modifications of the human NDN gene

Nucleic Acids Res. 2004 Jun 24;32(11):3376-82. doi: 10.1093/nar/gkh671. Print 2004.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Alleles
  • Autoantigens
  • Cell Line
  • Cells, Cultured
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Genomic Imprinting*
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Organ Specificity
  • Ribonucleoproteins, Small Nuclear / genetics
  • snRNP Core Proteins

Substances

  • Autoantigens
  • Histones
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Ribonucleoproteins, Small Nuclear
  • necdin
  • snRNP Core Proteins
  • Lysine