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

被引:45
作者
Lau, JCY [1 ]
Hanel, ML [1 ]
Wevrick, R [1 ]
机构
[1] Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
D O I
10.1093/nar/gkh671
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:3376 / 3382
页数:7
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