Large-scale human promoter mapping using CpG islands
Large-scale human promoter mapping using CpG islands
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DOI：
10.1038/79189
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发表时间：
2000-09-01
期刊：
影响因子：
30.8
通讯作者：
Zhang, MQ
中科院分区：
文献类型：
--
作者：
Ioshikhes, IP;Zhang, MQ
脊椎动物基因组DNA通常是CpG缺失的（1,2），可能是因为80%的CpG二核苷酸的胞嘧啶甲基化导致它们频繁突变为胸腺嘧啶。CpG转化为TpG二核苷酸(3)。然而，存在高G+C含量的基因组区域（CpG岛），其中CpG的发生率明显较高，接近预期频率，而甲基化浓度明显低于整个基因组(4)。CpG岛(5)长度超过200 bp， G+C含量和CpG频率超过50%，至少为统计预期的0.6。大约50%的哺乳动物基因启动子与一个或多个CpG岛相关(6)。尽管生物学家经常直观地使用CpG岛进行5'基因鉴定（7,8）。这还没有被严格量化(9)。我们已经确定了区分启动子相关和非相关CpG岛的特征。这导致了大规模启动子映射（2kb分辨率）的有效算法，启动子的假阳性预测浓度远低于以前获得的。使用该算法，我们在转录起始位点（TSS）周围的区间（-500到+1500）内正确区分了大约85%的CpG岛和远离TSS的CpG岛。我们还正确地绘制了大约93%含有CpG岛的启动子。
Vertebrate genomic DNA is generally CpG depleted(1,2), possibly because methylation of cytosines at 80% of CpG dinucleotides results in their frequent mutation to thymine. and thus CpG to TpG dinucleotides(3). There are, however, genomic regions of high G+C content (CpG islands), where the occurrence of CpGs is significantly higher, close to the expected frequency, whereas the methylation concentration is significantly lower than the overall genome(4). CpG islands(5) are longer than 200 bp and have over 50% of G+C content and CpG frequency, at least 0.6 of that statistically expected. Approximately 50% of mammalian gene promoters are associated with one or more CpG islands(6). Although biologists often intuitively use CpG islands for 5' gene identification(7,8). this has not been rigorously quantified(9). We have determined the features that discriminate the promoter-associated and non-associated CpG islands. This led to an effective algorithm for large-scale promoter mapping (with 2kb resolution) with a concentration of false-positive predictions of promoters much lower than previously obtained. Using this algorithm, we correctly discriminated approximately 85% of the CpG islands within an interval (-500 to +1500) around a transcriptional start site (TSS) from those that lie further away from TSSs. We also correctly mapped approximately 93% of the promoters containing CpG islands.