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

CG dinucleotide clustering is a species-specific property of the genome.
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DOI:
10.1093/nar/gkm489
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发表时间:
2007
影响因子:
14.9
通讯作者:
Greally JM
Greally JM
中科院分区:
生物学2区
文献类型:
--
作者:
Glass JL;Thompson RF;Khulan B;Figueroa ME;Olivier EN;Oakley EJ;Van Zant G;Bouhassira EE;Melnick A;Golden A;Fazzari MJ;Greally JM

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胞嘧啶-鸟嘌呤(CG)二核苷酸处的胞嘧啶是哺乳动物基因组中DNA甲基转移酶的几乎唯一的靶标。甲基胞嘧啶自发脱氨为胸腺嘧啶,使甲基化胞嘧啶异常容易发生突变和随之而来的消耗。其中CG二核苷酸保持相对富集的基因座,可能是由于其在生殖细胞周期期间的未甲基化状态,被称为CpG岛。目前,CpG岛仅由碱基组成标准定义,允许任何测序基因组的注释。使用一种新的生物信息学方法,我们表明,CG集群可以被确定为基因组序列的固有属性,而不施加一个基础组成的先验假设。我们还表明,CG集群共定位在人类基因组中的低甲基化位点和注释转录起始位点在更大程度上比以前的CpG岛定义产生的注释。此外,这种新的方法允许CG集群被确定在一个物种的特定方式,揭示了一定程度的orthopathic保护,这是不透露目前的基础组成的方法。最后,我们的方法是能够识别甲基化基因组(如红鳍东方鲀),完全缺乏CG聚类,它是不合适的注释CpG岛或CG簇。
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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