CPG ISLANDS IN VERTEBRATE GENOMES
CPG ISLANDS IN VERTEBRATE GENOMES
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DOI：
10.1016/0022-2836(87)90689-9
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发表时间：
1987-07-20
影响因子：
5.6
通讯作者：
FROMMER, M
中科院分区：
文献类型：
--
作者：
GARDINERGARDEN, M;FROMMER, M
虽然脊椎动物的DNA通常在二核苷酸CpG中缺失，但最近的研究表明，一些脊椎动物的基因含有CpG岛，即DNA中G+C含量较高的区域，以及相对于整体基因组而言CpG二核苷酸出现频率较高的区域。在这项研究中，对大量脊椎动物基因序列进行了筛选，以寻找CpG岛的存在。然后分析每个CpG岛的长度、核苷酸组成、CpG二核苷酸的频率以及相对于相关基因转录单位的位置。CpG岛与所有看家基因和许多组织特异性基因的5‘端以及一些组织特异性基因的3’端相关。一些基因同时含有5‘’和3‘’CpG岛，由数千个碱基对的CpG缺失的DNA隔开。5‘’CpG岛通过5‘-DNA、外显子和内含子延伸，而3“”CpG岛大多与外显子有关。在不同物种中，CpG岛通常位于与相同基因转录单位相同的位置，但也有一些显著的例外。研究了由GGGCGG序列或其反向互补CCGCCC组成的G/C盒相对于CpG岛的位置。G/C盒在CpG缺失的DNA中很少见，但在CpG岛中大量存在，它们出现在3‘’CpG岛上，以及5‘’CpG岛上，与组织特异性和家务基因相关。G/C盒位于转录起始点的上游和下游，带有5‘’CpG岛。因此，G/C盒似乎是CpG岛的一个特征，而不是管家基因启动子区域的特征。验证了维持CpG岛高频率的两种理论：尽管5mCpG有通过脱氨基突变为TPG+CPA的趋势，但在甲基化基因组中保持了CpG岛，仅靠高G+C含量的结构稳定性，以及与外显子相关的CpG岛是由精氨酸密码子CGX的某些选择性重要性造成的。这两种理论都不能解释CpG二核苷酸在所分析序列中的分布。讨论了CpG岛在转录和转录后基因表达调控中的可能功能，并与CpG岛在生殖系DNA中保持为“无甲基化区域”的理论有关。
Although vertebrate DNA is generally depleted in the dinucleotide CpG, it has recently been shown that some vertebrate genes contain CpG islands, regions of DNA with a high G + C content and a high frequency of CpG dinucleotides relative to the bulk genome. In this study, a large number of sequences of vertebrate genes were screenedfor the presence of CpG islands. Each CpG island was then analysed in terms of length, nucleotide composition, ferequency of CpG dinucleotides, and location relative to the transcription unit of the associated gene. CpG islands were associated with the 5'' ends of all housekeeping genes and many tissue-specific genes, and with the 3'' ends of some tissue-specific genes. A few genes contained both 5'' and 3'' CpG islands, separated by several thousand base-pairs of CpG-depleted DNA. The 5'' CpG islands extended through 5''-flanking DNA, exons and introns, whereas most of the 3'' CpG islands appeared to be associated with exons. CpG islands were generally found in the same position relative to the transcription unit of equivalent genes in different species, with some notable exceptions. The locations of G/C boxes, composed of the sequence GGGCGG or its reverse complement CCGCCC, were investigated relative to the location of CpG islands. G/C boxes were found to be rare in CpG-depleted DNA and plentiful in CpG islands, where they occurred in 3'' CpG islands, as well as in 5'' CpG islands associated with tissue-specific and housekeeping genes. G/C boxes were located both upstream and downstream from the transcription start site of genes with 5'' CpG islands. Thus, G/C boxes appeared to be a feature of CpG islands in general, rather than a feature of the promoter region of housekeeping genes. Two theories for the maintenance of a high frequency of CpG dinucleotides in CpG islands were tested: that CpG islands in methylated genomes are maintained, despite a tendency for 5mCpG to mutate by deamination to TpG + CpA, by the structural stability of a high G + C content alone, and that CpG islands associated with exons result from some selective importance of the arginine codon CGX. Neither of these theories could account for the distribution of CpG dinucleotides in the sequences analyzed. Possible functions of CpG islands in transcriptional and post-transcriptional regulation of gene expression were discussed, and were related to theories for the maintenance of CpG islands as "methylation-free zones" in germline DNA.