Sequence determinants, function, and evolution of CpG islands.
Sequence determinants, function, and evolution of CpG islands.
复制标题
DOI：
10.1042/bst20200695
复制
发表时间：
2021-06-30
影响因子：
3.9
通讯作者：
Bogdanovic O
中科院分区：
文献类型：
--
作者：
Angeloni A;Bogdanovic O
在脊椎动物中，胞嘧啶-鸟嘌呤（cytosine-guanine，CpG）二核苷酸主要是甲基化的，约80%的CpG位点含有5-甲基胞嘧啶（5-methylcytosine，5 mC），这是一种与长期基因沉默相关的抑制标记。这种全局高甲基化状态的例外是称为CpG岛（CGI）的富含CpG的DNA序列，其相对于大部分基因组大多是低甲基化的。CGIs重叠启动子从最早的脊椎动物到人类，表明一致的进化驱动兼容CGI保留。CGIs的特征在于DNA序列特征，包括DNA低甲基化、CpG和GC含量升高以及转录因子结合位点的存在。这些序列特征与转录因子和染色质修饰酶的募集以及一般的转录激活一致。CGIs与高甲基化脊椎动物基因组中的转录起始位点共定位，然而，越来越多的证据表明CGIs可能在其他基因组环境中发挥其基因调控功能。在这篇综述中，我们讨论了CGIs的不同监管功能，其功能读出，并与CGI保留在脊椎动物和可能在无脊椎动物的进化意义。
In vertebrates, cytosine-guanine (CpG) dinucleotides are predominantly methylated, with ∼80% of all CpG sites containing 5-methylcytosine (5mC), a repressive mark associated with long-term gene silencing. The exceptions to such a globally hypermethylated state are CpG-rich DNA sequences called CpG islands (CGIs), which are mostly hypomethylated relative to the bulk genome. CGIs overlap promoters from the earliest vertebrates to humans, indicating a concerted evolutionary drive compatible with CGI retention. CGIs are characterised by DNA sequence features that include DNA hypomethylation, elevated CpG and GC content and the presence of transcription factor binding sites. These sequence characteristics are congruous with the recruitment of transcription factors and chromatin modifying enzymes, and transcriptional activation in general. CGIs colocalize with sites of transcriptional initiation in hypermethylated vertebrate genomes, however, a growing body of evidence indicates that CGIs might exert their gene regulatory function in other genomic contexts. In this review, we discuss the diverse regulatory features of CGIs, their functional readout, and the evolutionary implications associated with CGI retention in vertebrates and possibly in invertebrates.