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Nucleic Acids Research 2004 32(11):3376-3382; doi:10.1093/nar/gkh671
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Published online 24 June 2004

Nucleic Acids Research, Vol. 32 No. 11 © Oxford University Press 2004; all rights reserved

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

Jason C. Y. Lau, Meredith L. Hanel and Rachel Wevrick*

Department of Medical Genetics, 8-42 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

* To whom correspondence should be addressed. Tel: +1 780 492 7908; Fax: +1 780 492 1998; Email: rachel.wevrick{at}ualberta.ca

Received April 10, 2004; Revised and Accepted June 8, 2004

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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