Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation

Wong, Nicholas C, Wong, Lee H, Quach, Julie M, Canham, Paul, Craig, Jeffrey M, Song, Jenny Z, Clark, Susan J and Choo, KH Andy 2006, Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation, PLoS genetics, vol. 2, no. 2, pp. 0172-0186, doi: 10.1371/journal.pgen.0020017.

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Title Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation
Author(s) Wong, Nicholas C
Wong, Lee H
Quach, Julie M
Canham, Paul
Craig, Jeffrey MORCID iD for Craig, Jeffrey M orcid.org/0000-0003-3979-7849
Song, Jenny Z
Clark, Susan J
Choo, KH Andy
Journal name PLoS genetics
Volume number 2
Issue number 2
Article ID e17
Start page 0172
End page 0186
Total pages 15
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2006-02
ISSN 1553-7390
1553-7404
Keyword(s) Animals
CHO Cells
Centromere
Chromatin
CpG Islands
Cricetinae
DNA Methylation
Genome
Mice
Transcription, Genetic
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Summary DNA methylation is a hallmark of transcriptional silencing, yet transcription has been reported at the centromere. To address this apparent paradox, we employed a fully sequence-defined ectopic human centromere (or neocentromere) to investigate the relationship between DNA methylation and transcription. We used sodium bisulfite PCR and sequencing to determine the methylation status of 2,041 CpG dinucleotides distributed across a 6.76-Mbp chromosomal region containing a neocentromere. These CpG dinucleotides were associated with conventional and nonconventional CpG islands. We found an overall hypermethylation of the neocentric DNA at nonconventional CpG islands that we designated as CpG islets and CpG orphans. The observed hypermethylation was consistent with the presence of a presumed transcriptionally silent chromatin state at the neocentromere. Within this neocentric chromatin, specific sites of active transcription and the centromeric chromatin boundary are defined by DNA hypomethylation. Our data demonstrate, for the first time to our knowledge, a correlation between DNA methylation and centromere formation in mammals, and that transcription and "chromatin-boundary activity" are permissible at the centromere through the selective hypomethylation of pockets of sequences without compromising the overall silent chromatin state and function of the centromere.
Language eng
DOI 10.1371/journal.pgen.0020017
Field of Research 0604 Genetics
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, Wong et al.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30119189

Document type: Journal Article
Collections: School of Medicine
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