Tissue-specific and imprinted epigenetic modifications of the human NDN gene.
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.
Lau
Jason C Y
JC
Department of Medical Genetics, 8-42 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Hanel
Meredith L
ML
Wevrick
Rachel
R
D000107:Acetylation; D000483:Alleles; D001324:Autoantigens; D002460:Cell Line; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009928:Organ Specificity; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D055517:snRNP Core Proteins
D001324:Autoantigens; D006657:Histones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017411:Ribonucleoproteins, Small Nuclear; C069766:necdin; D055517:snRNP Core Proteins; D008239:Lysine