Functional Relevance of CpG Island Length for Regulation of Gene Expression
Functional Relevance of CpG Island Length for Regulation of Gene Expression
复制标题
DOI：
10.1534/genetics.110.126094
复制
发表时间：
2011-04-01
期刊：
影响因子：
3.3
通讯作者：
Yi, Soojin V.
中科院分区：
文献类型：
--
作者：
Elango, Navin;Yi, Soojin V.
CpG 岛标记了 CpG 丰富的脊椎动物基因组中的 CpG 富集区域。虽然 CpG 岛的监管重要性已被广泛接受，但人们很少意识到 CpG 岛的长度差异很大。例如，人类基因组中的 CpG 岛长度相差近 30 倍。在这里，我们报告的研究结果表明 CpG 岛的长度具有功能性影响。具体来说，我们表明与长 CpG 岛相关的启动子（长 CGI 启动子）与其他启动子不同。首先，长 CGI 启动子与具有中等水平基因表达宽度的基因独特相关。值得注意的是，从信息内容的角度来看，中间表达宽度需要最复杂的基因调控模式。其次，长 CGI 启动子比其他启动子编码更多的 RNA 聚合酶 II (Polr2a) 结合位点。第三，与其他 CGI 启动子相比，长 CGI 启动子中 Polr2a 的实际结合模式以更具组织特异性的方式发生。此外，与其他启动子相比，长CGI启动子含有最多数量的实验表征的转录起始位点，并且其中的转录起始位点类型偏向于基因表达的组织特异性模式。最后，长 CGI 启动子优先与参与发育和调控的基因相关。总之，这些发现表明 CpG 岛存在功能相关的变异。通过研究某些 CpG 岛特征的后果，我们可以获得对基因表达调控复杂性的机制和进化的更多见解。
CpG islands mark CpG-enriched regions in otherwise CpG-depleted vertebrate genomes. While the regulatory importance of CpG islands is widely accepted, it is little appreciated that CpG islands vary greatly in lengths. For example, CpG islands in the human genome vary similar to 30-fold in their lengths. Here we report findings suggesting that the lengths of CpG islands have functional consequences. Specifically, we show that promoters associated with long CpG islands (long-CGI promoters) are distinct from other promoters. First, long-CGI promoters are uniquely associated with genes with an intermediate level of gene expression breadths. Notably, intermediate expression breadths require the most complex mode of gene regulation, from the standpoint of information content. Second, long-CGI promoters encode more RNA polymerase II (Polr2a) binding sites than other promoters. Third, the actual binding patterns of Polr2a occur in a more tissue-specific manner in long-CGI promoters compared to other CGI promoters. Moreover, long-CGI promoters contain the largest numbers of experimentally characterized transcription start sites compared to other promoters, and the types of transcription start sites in them are biased toward tissue-specific patterns of gene expression. Finally, long-CGI promoters are preferentially associated with genes involved in development and regulation. Together, these findings indicate that functionally relevant variations of CpG islands exist. By investigating consequences of certain CpG island traits, we can gain additional insights into the mechanism and evolution of regulatory complexity of gene expression.