craig-permissivetranscriptional-2006.pdf (598.47 kB)
Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation
journal contribution
posted on 2006-02-01, 00:00 authored by Nicholas C Wong, Lee H Wong, Julie M Quach, Paul Canham, Jeffrey CraigJeffrey Craig, Jenny Z Song, Susan J Clark, K H Andy ChooDNA 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.
History
Journal
PLoS geneticsVolume
2Issue
2Article number
e17Pagination
0172 - 0186Publisher
Public Library of ScienceLocation
San Francisco, Calif.Publisher DOI
Link to full text
ISSN
1553-7390eISSN
1553-7404Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2006, Wong et al.Usage metrics
Categories
Keywords
AnimalsCHO CellsCentromereChromatinCpG IslandsCricetinaeDNA MethylationGenomeMiceTranscription, GeneticScience & TechnologyLife Sciences & BiomedicineGenetics & HeredityH3 LYSINE-9 METHYLATIONCPG-ISLANDSALPHA-SATELLITETRANSPOSABLE ELEMENTSCYTOSINE METHYLATIONCHROMATIN-STRUCTUREBINDING DOMAINHISTONEHETEROCHROMATINGENEGenetics
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC