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CG dinucleotide clustering is a species-specific property of the genome

Cytosines at cytosine-guanine (CG) dinucleotides are the near-exclusive target of DNA methyltransferases in mammalian genomes. Spontaneous deamination of methylcytosine to thymine makes methylated cytosines unusually susceptible to mutation and consequent depletion. The loci where CG dinucleotides r...

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Autores principales: Glass, Jacob L., Thompson, Reid F., Khulan, Batbayar, Figueroa, Maria E., Olivier, Emmanuel N., Oakley, Erin J., Van Zant, Gary, Bouhassira, Eric E., Melnick, Ari, Golden, Aaron, Fazzari, Melissa J., Greally, John M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175314/
https://www.ncbi.nlm.nih.gov/pubmed/17932072
http://dx.doi.org/10.1093/nar/gkm489
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author Glass, Jacob L.
Thompson, Reid F.
Khulan, Batbayar
Figueroa, Maria E.
Olivier, Emmanuel N.
Oakley, Erin J.
Van Zant, Gary
Bouhassira, Eric E.
Melnick, Ari
Golden, Aaron
Fazzari, Melissa J.
Greally, John M.
author_facet Glass, Jacob L.
Thompson, Reid F.
Khulan, Batbayar
Figueroa, Maria E.
Olivier, Emmanuel N.
Oakley, Erin J.
Van Zant, Gary
Bouhassira, Eric E.
Melnick, Ari
Golden, Aaron
Fazzari, Melissa J.
Greally, John M.
author_sort Glass, Jacob L.
collection PubMed
description Cytosines at cytosine-guanine (CG) dinucleotides are the near-exclusive target of DNA methyltransferases in mammalian genomes. Spontaneous deamination of methylcytosine to thymine makes methylated cytosines unusually susceptible to mutation and consequent depletion. The loci where CG dinucleotides remain relatively enriched, presumably due to their unmethylated status during the germ cell cycle, have been referred to as CpG islands. Currently, CpG islands are solely defined by base compositional criteria, allowing annotation of any sequenced genome. Using a novel bioinformatic approach, we show that CG clusters can be identified as an inherent property of genomic sequence without imposing a base compositional a priori assumption. We also show that the CG clusters co-localize in the human genome with hypomethylated loci and annotated transcription start sites to a greater extent than annotations produced by prior CpG island definitions. Moreover, this new approach allows CG clusters to be identified in a species-specific manner, revealing a degree of orthologous conservation that is not revealed by current base compositional approaches. Finally, our approach is able to identify methylating genomes (such as Takifugu rubripes) that lack CG clustering entirely, in which it is inappropriate to annotate CpG islands or CG clusters.
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spelling pubmed-21753142008-01-07 CG dinucleotide clustering is a species-specific property of the genome Glass, Jacob L. Thompson, Reid F. Khulan, Batbayar Figueroa, Maria E. Olivier, Emmanuel N. Oakley, Erin J. Van Zant, Gary Bouhassira, Eric E. Melnick, Ari Golden, Aaron Fazzari, Melissa J. Greally, John M. Nucleic Acids Res Genomics Cytosines at cytosine-guanine (CG) dinucleotides are the near-exclusive target of DNA methyltransferases in mammalian genomes. Spontaneous deamination of methylcytosine to thymine makes methylated cytosines unusually susceptible to mutation and consequent depletion. The loci where CG dinucleotides remain relatively enriched, presumably due to their unmethylated status during the germ cell cycle, have been referred to as CpG islands. Currently, CpG islands are solely defined by base compositional criteria, allowing annotation of any sequenced genome. Using a novel bioinformatic approach, we show that CG clusters can be identified as an inherent property of genomic sequence without imposing a base compositional a priori assumption. We also show that the CG clusters co-localize in the human genome with hypomethylated loci and annotated transcription start sites to a greater extent than annotations produced by prior CpG island definitions. Moreover, this new approach allows CG clusters to be identified in a species-specific manner, revealing a degree of orthologous conservation that is not revealed by current base compositional approaches. Finally, our approach is able to identify methylating genomes (such as Takifugu rubripes) that lack CG clustering entirely, in which it is inappropriate to annotate CpG islands or CG clusters. Oxford University Press 2007-11 2007-10-10 /pmc/articles/PMC2175314/ /pubmed/17932072 http://dx.doi.org/10.1093/nar/gkm489 Text en © 2007 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genomics
Glass, Jacob L.
Thompson, Reid F.
Khulan, Batbayar
Figueroa, Maria E.
Olivier, Emmanuel N.
Oakley, Erin J.
Van Zant, Gary
Bouhassira, Eric E.
Melnick, Ari
Golden, Aaron
Fazzari, Melissa J.
Greally, John M.
CG dinucleotide clustering is a species-specific property of the genome
title CG dinucleotide clustering is a species-specific property of the genome
title_full CG dinucleotide clustering is a species-specific property of the genome
title_fullStr CG dinucleotide clustering is a species-specific property of the genome
title_full_unstemmed CG dinucleotide clustering is a species-specific property of the genome
title_short CG dinucleotide clustering is a species-specific property of the genome
title_sort cg dinucleotide clustering is a species-specific property of the genome
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175314/
https://www.ncbi.nlm.nih.gov/pubmed/17932072
http://dx.doi.org/10.1093/nar/gkm489
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