Wachter Elisabeth, Quante Timo, Merusi Cara, Arczewska Aleksandra, Stewart Francis, Webb Shaun, Bird Adrian
The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Genomics and Biotechnology Centre, Technische Universitaet Dresden, Dresden, Germany.
Elife. 2014 Sep 26;3:e03397. doi: 10.7554/eLife.03397.
The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display 'active' histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a 'bivalent' chromatin state bearing simultaneous 'active' and 'inactive' chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs.
哺乳动物基因组中散布着CpG岛（CGIs），它们与大部分基因组有显著差异，富含鸟嘌呤和胞嘧啶（G + C）以及二核苷酸CpG。CpG岛通常包含转录起始位点，并显示出“活跃”的组蛋白标记，尤其是组蛋白H3赖氨酸4甲基化。在胚胎干细胞（ESCs）中，一些CpG岛呈现出一种“双价”染色质状态，同时带有“活跃”和“不活跃”的染色质标记。为了确定CpG岛染色质是在特定基因处进行发育编程，还是由CpG岛DNA的共同特征所决定，我们将人工合成的类似CpG岛的DNA序列整合到胚胎干细胞基因组中。我们发现，双价性是富含CpG、富含G + C的DNA的默认染色质结构。仅高CpG密度不足以产生这种效应，因为富含腺嘌呤和胸腺嘧啶（A + T）的序列环境总是会引发从头DNA甲基化，导致CpG岛标志性染色质的丢失。我们得出结论，在CpG岛处诱导标志性染色质结构既需要富含CpG，也需要富含G + C。
