Identification of alternative topological domains in chromatin.

Identification of alternative topological domains in chromatin.
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鉴定染色质中替代拓扑结构域。

DOI:
10.1186/1748-7188-9-14
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发表时间:
2014
期刊:
Algorithms for molecular biology : AMB
影响因子:
--
通讯作者:
Kingsford C
Kingsford C
中科院分区:
其他
文献类型:
--
作者:
Filippova D;Patro R;Duggal G;Kingsford C

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染色体构象捕获实验已经发现了密集的、连续的、兆碱基大小的拓扑结构域,这些拓扑结构域在细胞类型之间是相似的,并且在物种之间是保守的。这些结构域与许多染色质标记物密切相关,并且已经被包括在许多分析中。然而,功能相关的域可能存在于多个长度尺度。我们引入了一个新的和有效的算法,能够捕捉持久域在不同的分辨率,通过调整一个单一的尺度参数。我们识别的域的集合使我们能够量化域结构的层次化程度,而不是重叠,我们的分析揭示了一个明显的层次结构,其中较大的稳定域往往完全包含较小的域。所鉴定的新结构域与先前报道的结构域有很大不同,并且高度富集绝缘因子CTCF结合和边界处的组蛋白标记。
Chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types and conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally-relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across various resolutions by adjusting a single scale parameter. The ensemble of domains we identify allows us to quantify the degree to which the domain structure is hierarchical as opposed to overlapping, and our analysis reveals a pronounced hierarchical structure in which larger stable domains tend to completely contain smaller domains. The identified novel domains are substantially different from domains reported previously and are highly enriched for insulating factor CTCF binding and histone marks at the boundaries.
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