Rollins, R. A., Haghighi, F., Edwards, J. R., Das, Rajdeep, Zhang, M. Q., Ju, J., Bestor, T. H. (2006) Large-scale structure of genomic methylation patterns. Genome Research, 16 (2). pp. 157-163. ISSN 10889051
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Abstract
The mammalian genome depends on patterns of methylated cytosines for normal function, but the relationship between genomic methylation patterns and the underlying sequence is unclear. We have characterized the methylation landscape of the human genome by global analysis of patterns of CpG depletion and by direct sequencing of 3073 unmethylated domains and 2565 methylated domains from human brain DNA. The genome was found to consist of short (<4 kb) unmethylated domains embedded in a matrix of long methylated domains. Unmethylated domains were enriched in promoters, CpG islands, and first exons, while methylated domains comprised interspersed and tandem-repeated sequences, exons other than first exons, and non-annotated single-copy sequences that are depleted in the CpG dinucleotide. The enrichment of regulatory sequences in the relatively small unmethylated compartment suggests that cytosine methylation constrains the effective size of the genome through the selective exposure of regulatory sequences. This buffers regulatory networks against changes in total genome size and provides an explanation for the C value paradox, which concerns the wide variations in genome size that scale independently of gene number. This suggestion is compatible with the finding that cytosine methylation is universal among large-genome eukaryotes, while many eukaryotes with genome sizes <5 × 108 bp do not methylate their DNA. ©2006 by Cold Spring Harbor Laboratory Press.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | DNA methylation genomics CpG Islands DNA Methylation Genome, Human Eukaryota Mammalia |
| Subjects: | bioinformatics > genomics and proteomics > Mapping and Rendering organs, tissues, organelles, cell types and functions > organs types and functions > brain bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation |
| CSHL Authors: | |
| Communities: | CSHL labs > Zhang lab |
| Depositing User: | CSHL Librarian |
| Date: | 2006 |
| Date Deposited: | 08 Dec 2011 20:54 |
| Last Modified: | 27 Apr 2018 15:37 |
| PMCID: | PMC1361710 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22888 |
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