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Nucleic Acids Research Advance Access originally published online on October 10, 2007
Nucleic Acids Research 2007 35(20):6798-6807; doi:10.1093/nar/gkm489
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Nucleic Acids Research, 2007, Vol. 35, No. 20 6798-6807
© 2007 The Author(s)
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.

Genomics

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

Jacob L. Glass1, Reid F. Thompson1, Batbayar Khulan1, Maria E. Figueroa2, Emmanuel N. Olivier3, Erin J. Oakley4, Gary Van Zant4, Eric E. Bouhassira3,5, Ari Melnick2, Aaron Golden6, Melissa J. Fazzari7 and John M. Greally1,5,*

1Department of Molecular Genetics, 2Department of Developmental and Molecular Biology and 3Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA, 4Division of Hematology/Oncology, University of Kentucky, Markey Cancer Center, 800 Rose Street, Lexington KY 40536, USA, 5Department of Medicine (Hematology), Albert Einstein College of Medicine, Bronx, NY 10461, USA, 6Department of Information Technology, National University of Ireland Galway, Newcastle Road, Galway, Republic of Ireland and 7Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA

*To whom correspondence should be addressed. Tel: +1 718 430 2875; Fax: +1 718 824 3153; Email: jgreally{at}aecom.yu.edu

Received February 9, 2007. Revised May 23, 2007. Accepted June 6, 2007.

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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