Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions
Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions
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DOI：
10.1038/ng1891
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发表时间：
2006-11-01
期刊：
影响因子：
30.8
通讯作者：
Ohlsson, Rolf
中科院分区：
文献类型：
--
作者：
Zhao, Zhihu;Tavoosidana, Gholamreza;Ohlsson, Rolf
积累的证据收敛的可能性，染色体相互作用，以调节转录的反式。系统地探讨这种相互作用的表观遗传方面，我们设计了一种策略，称为环状染色体构象捕获（4C）。这种方法涉及环化步骤，其使得能够高通量筛选染色体之间的物理相互作用，而无需对相互作用伴侣的先入为主的想法。在这里，我们确定了114个独特的序列，从所有的常染色体，其中几个相互作用主要与母系遗传的H19印迹控制区。印迹结构域在4C序列库中的比例过高，进一步突出了这些相互作用的表观遗传性质。此外，我们发现，差异甲基化区域之间的直接相互作用与转录的表观遗传调控反式。最后，特定于母体H19印迹控制区的相互作用模式在胚胎干细胞体外成熟过程中进行重编程。这些观察为发育、癌症表观遗传学和印记的进化提供了新的线索。
Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughput screening of physical interactions between chromosomes without a preconceived idea of the interacting partners. Here we identify 114 unique sequences from all autosomes, several of which interact primarily with the maternally inherited H19 imprinting control region. Imprinted domains were strongly overrepresented in the library of 4C sequences, further highlighting the epigenetic nature of these interactions. Moreover, we found that the direct interaction between differentially methylated regions was linked to epigenetic regulation of transcription in trans. Finally, the patterns of interactions specific to the maternal H19 imprinting control region underwent reprogramming during in vitro maturation of embryonic stem cells. These observations shed new light on development, cancer epigenetics and the evolution of imprinting.