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

被引:62
作者
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. [1 ]
机构
[1] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[4] Univ Kentucky, Div Hematol Oncol, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA
[5] Albert Einstein Coll Med, Dept Med Hematol, Bronx, NY 10461 USA
[6] Natl Univ Ireland Univ Coll Galway, Dept Informat Technol, Galway, Ireland
[7] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA
关键词
D O I
10.1093/nar/gkm489
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6798 / 6807
页数:10
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