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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Lau JC,Hanel ML,Wevrick R

doi

10.1093/nar/gkh671

keywords:

subject

Has Abstract

pub_date

2004-06-24 00:00:00

pages

3376-82

issue

11

eissn

0305-1048

issn

1362-4962

pii

32/11/3376

journal_volume

32

pub_type

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