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  DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution.

Zhang, Y., Rohde, C., Tierlin, S., Jurkowski, T. P., Bock, C., Santacruz, D., et al. (2009). DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution. PLoS Genetics, 5(3), e1000438-e1000438. doi:10.1371/journal.pgen.1000438.

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Genre: Journal Article
Alternative Title : PLoS genet

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 Creators:
Zhang, Yingying, Author
Rohde, Christian, Author
Tierlin, Sascha, Author
Jurkowski, Tomasz P., Author
Bock, Christoph1, Author
Santacruz, Diana, Author
Ragozin, Sergey, Author
Reinhardt, Richard2, Author              
Groth, Marco, Author
Walter, Jörn3, Author              
Jeltsch, Albert, Author
Affiliations:
1Max Planck Society, ou_persistent13              
2High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433552              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: Differential DNA methylation is an essential epigenetic signal for gene regulation, development, and disease processes. We mapped DNA methylation patterns of 190 gene promoter regions on chromosome 21 using bisulfite conversion and subclone sequencing in five human cell types. A total of 28,626 subclones were sequenced at high accuracy using (long-read) Sanger sequencing resulting in the measurement of the DNA methylation state of 580427 CpG sites. Our results show that average DNA methylation levels are distributed bimodally with enrichment of highly methylated and unmethylated sequences, both for amplicons and individual subclones, which represent single alleles from individual cells. Within CpG-rich sequences, DNA methylation was found to be anti-correlated with CpG dinucleotide density and GC content, and methylated CpGs are more likely to be flanked by AT-rich sequences. We observed over-representation of CpG sites in distances of 9, 18, and 27 bps in highly methylated amplicons. However, DNA sequence alone is not sufficient to predict an amplicon's DNA methylation status, since 43% of all amplicons are differentially methylated between the cell types studied here. DNA methylation in promoter regions is strongly correlated with the absence of gene expression and low levels of activating epigenetic marks like H3K4 methylation and H3K9 and K14 acetylation. Utilizing the single base pair and single allele resolution of our data, we found that i) amplicons from different parts of a CpG island frequently differ in their DNA methylation level, ii) methylation levels of individual cells in one tissue are very similar, and iii) methylation patterns follow a relaxed site-specific distribution. Furthermore, iv) we identified three cases of allele-specific DNA methylation on chromosome 21. Our data shed new light on the nature of methylation patterns in human cells, the sequence dependence of DNA methylation, and its function as epigenetic signal in gene regulation. Further, we illustrate genotype–epigenotype interactions by showing novel examples of allele-specific methylation.

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Language(s): eng - English
 Dates: 2009-03-27
 Publication Status: Published in print
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Title: PLoS Genetics
  Alternative Title : PLoS genet
Source Genre: Journal
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Pages: - Volume / Issue: 5 (3) Sequence Number: - Start / End Page: e1000438 - e1000438 Identifier: ISSN: 1553-7390