Genomic landscape of CpG rich elements in human.
Genomic landscape of CpG rich elements in human.
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DOI：
10.1186/s12862-016-0864-0
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发表时间：
2017-02-07
影响因子：
3.4
通讯作者：
Orlov YL
中科院分区：
文献类型：
--
作者：
Babenko VN;Chadaeva IV;Orlov YL
CpG岛（CGI）和Alu元件在基因组中的功能、进化和分布的研究始于20世纪80年代（1981、1986年）。其高度偏斜的基因组分布暗示非随机反转录转座模式。除了基因启动子中的CGIs外，在同源框基因区域和大卫星中也观察到了CGIs簇，但对其分布特征的整体情况还没有掌握。试图确定其（全基因组）分布的任何致病特征，如DNA背景介导的Alu重复序列的优选插入位点，已被归因于其簇的位置。最近出现的人类基因组的高分辨率3D图谱允许将基因组分离成天然可观察到的核亚区的大尺度染色质结构域，或拓扑相关结构域（TADs），其通过染色质空间分布来指定。我们利用染色质图谱来阐明大尺度染色质状态与CpG富集元素景观之间的关系。在分析的过程中，证实了基因，Alu和CGI簇保持明显的，尽管强度不同，对开放染色质的偏好。首次清楚地表明，Alu和CGIs的簇密度单调地依赖于染色质可及率。特别是，这些元件的最高密度出现在A1常染色质区域，其特征是在S期早期复制的小长度基因的高密度。这意味着这些元件介导（CGIs）或作为染色质可及性的辅助元件（Alus）。我们阐明了甲基化和非甲基化的CGIs都显示出对染色质可及性的亲和力。作为比较基因组学部分的一部分，我们阐明了狗的基因组非典型结构，在哺乳动物中表现突出，因为其与基因数量相比具有高的CGIs丰度，这是通过在具有高度偏斜的CG含量的亚端粒和近着丝粒区域中存在密集串联CGI扩展热点（平均500 kb）来解释的，而不是通过CGIs全局分布模式转变来解释的。这项研究强调了CG丰富的元素分布与新引入的大规模染色质状态图的密切联系，提出了上述基因组元素和染色质状态的相互关系的一个精炼的观点。根据我们的专业知识，研究中采用的TAD相关分区模型可能是关于全基因组染色质/等着丝粒图中CpG富集簇分布的最重要的模型。本文的在线版本（doi：10.1186/s12862-016-0864-0）包含补充材料，可供授权用户使用。
The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location. Recent emergence of high resolution 3D map of human genome allowed segregating the genome into the large scale chromatin domains of naturally observable nuclear subcompartments, or Topologically Associated Domains (TADs), designated by spatial chromatin distribution. We utilized the chromatin map to elucidate relations between large scale chromatin state and CpG rich elements landscape. In the course of analysis it was confirmed that genes, Alu and CGI clusters maintain obvious, albeit different in strength, preference for open chromatin. For the first time it was clearly shown that the clusters density of the Alu and CGIs monotonically depend on the chromatin accessibility rate. In particular, the highest density of these elements is found in A1 euchromatin regions characterized by a high density of small length genes replicating in the early S-phase. It implies that these elements mediate (CGIs) or are a side element (Alus) of chromatin accessibility. We elucidated that both methylated and non-methylated CGIs display the affinity to chromatin accessibility. As a part of comparative genomics section, we elucidated that the dog’s genome non-canonical structure, outstanding in mammals for its high CGIs abundance compared to gene number, is explained by the presence of dense tandem CGI extended hotspots (500 kb on average) in subtelomeric and pericentromeric regions with highly skewed CG content, and not by CGIs global distribution pattern shift. The study underlines the close association of CG-rich elements distribution with the newly introduced large scale chromatin state map, proposing a refined standpoint on interrelation of aforementioned genome elements and the chromatin state. To our expertise, the TAD-associated partition model employed in the study is likely the most substantial one regarding CpG rich clusters distribution among the whole genome chromatin/isochores maps available. The online version of this article (doi:10.1186/s12862-016-0864-0) contains supplementary material, which is available to authorized users.