Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features.

Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features.
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DOI:
10.1038/s41467-018-06664-6
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发表时间:
2018-10-11
影响因子:
16.6
通讯作者:
Peng W
Peng W
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kai Y;Andricovich J;Zeng Z;Zhu J;Tzatsos A;Peng W

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CCCTC结合的锌指蛋白(CTCF)介导的染色质远程相互作用网络对于基因组的组织和功能是重要的。虽然这个网络被认为在很大程度上是不变的,但我们发现它表现出广泛的细胞类型特定的相互作用,这有助于细胞特性。在这里,我们提出了棒棒糖,一个机器学习框架,它使用基因组和表观基因组特征预测CTCF介导的远程相互作用。使用CHIA-PET数据作为基准,我们证明了棒棒糖准确地预测了CTCF介导的细胞类型内和细胞类型之间的染色质相互作用,并且优于其他仅基于CTCF基序方向的方法。通过染色质构象捕获(3C)从计算和实验上证实了预测。此外,我们的方法确定了CTCF介导的染色质连接的其他决定因素,例如环内的基因表达。我们的研究有助于更好地理解CTCF介导的染色质相互作用的基本原理及其对基因表达的影响。CTCF介导染色质的长距离相互作用,这对基因组的组织和功能是重要的。在这里,作者证明了CTCF介导的相互作用组具有广泛的可塑性,并提出了棒棒糖,这是一个机器学习框架,利用基因组和表观基因组学特征预测CTCF介导的远程相互作用。
The CCCTC-binding zinc-finger protein (CTCF)-mediated network of long-range chromatin interactions is important for genome organization and function. Although this network has been considered largely invariant, we find that it exhibits extensive cell-type-specific interactions that contribute to cell identity. Here, we present Lollipop, a machine-learning framework, which predicts CTCF-mediated long-range interactions using genomic and epigenomic features. Using ChIA-PET data as benchmark, we demonstrate that Lollipop accurately predicts CTCF-mediated chromatin interactions both within and across cell types, and outperforms other methods based only on CTCF motif orientation. Predictions are confirmed computationally and experimentally by Chromatin Conformation Capture (3C). Moreover, our approach identifies other determinants of CTCF-mediated chromatin wiring, such as gene expression within the loops. Our study contributes to a better understanding about the underlying principles of CTCF-mediated chromatin interactions and their impact on gene expression. CTCF mediates long-range chromatin interactions which are important for genome organization and function. Here, the authors demonstrate that CTCF-mediated interactome exhibits extensive plasticity and present Lollipop, a machine-learning framework which predicts CTCF-mediated long-range interactions using genomic and epigenomic features.
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