Hi-C: a comprehensive technique to capture the conformation of genomes.
Hi-C: a comprehensive technique to capture the conformation of genomes.
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DOI：
10.1016/j.ymeth.2012.05.001
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发表时间：
2012-11
期刊：
影响因子：
4.8
通讯作者：
Dekker, Job
中科院分区：
文献类型：
--
作者：
Belton, Jon-Matthew;McCord, Rachel Patton;Gibcus, Johan Harmen;Naumova, Natalia;Zhan, Ye;Dekker, Job
我们描述了一种方法，Hi-C，来全面检测哺乳动物细胞核中的染色质相互作用。这种方法是基于染色体构象捕获的，因为染色质与甲醛交联，然后消化，并以这样一种方式重新连接，即只有共价连接在一起的DNA片段才形成连接产物。连接产物不仅包含它们在基因组序列中起源的信息，而且还包含它们在基因组3D组织中的物理位置的信息。在Hi-C中，生物素标记的核苷酸被结合在连接连接处，使得在修改DNA分子进行深度测序时能够丰富嵌合DNA连接连接处。Hi-C与下一代测序平台的兼容性使其能够以前所未有的规模检测染色质相互作用。这一进展使Hi-C有能力探索染色质生物物理学以及染色质结构在核生物功能中的含义。染色质相互作用的大规模平行调查为其他基因组研究提供了以前缺失的空间背景维度。这一空间背景将为染色质及其在正常条件下和疾病中的基因组调控中的作用的研究提供一个新的视角。
We describe a method, Hi-C, to comprehensively detect chromatin interactions in the mammalian nucleus. This method is based on Chromosome Conformation Capture, in that chromatin is crosslinked with formaldehyde, then digested, and re-ligated in such a way that only DNA fragments that are covalently linked together form ligation products. The ligation products contain the information of not only where they originated from in the genomic sequence but also where they reside, physically, in the 3D organization of the genome. In Hi-C, a biotin-labeled nucleotide is incorporated at the ligation junction, making it possible to enrich for chimeric DNA ligation junctions when modifying the DNA molecules for deep sequencing. The compatibility of Hi-C with next generation sequencing platforms makes it possible to detect chromatin interactions on an unprecedented scale. This advance gives Hi-C the power to both explore the chromatin biophysics as well as the implications of chromatin structure in the biological functions of the nucleus. A massively parallel survey of chromatin interaction provides the previously missing dimension of spatial context to other genomic studies. This spatial context will provide a new perspective to studies of chromatin and its role in genome regulation in normal conditions and in disease.
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