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新技术揭示细胞核染色质的放射状结构
作者:小柯机器人 发布时间:2020/5/28 12:59:45

瑞典卡罗林斯卡学院Magda Bienko、Nicola Crosetto等研究人员合作利用GPSeq技术来揭示了细胞核中染色质的放射状结构。这一研究成果于2020年5月25日在线发表在《自然—生物技术》上。

研究人员报道了通过测序进行基因座定位的方法(GPSeq),这是一种全基因组方法,可推断整个核半径上与核纤层的距离。GPSeq依赖于从核纤层到核中心的染色质逐步限制性消化,然后对产生的切割位点进行测序。使用GPSeq,研究人员以100 kb的分辨率绘制了人类基因组的径向组织图谱,从而揭示了基因组和表观基因组特征与基因表达以及A和B亚区室的径向模式。

通过结合径向信息和Hi-C测量的染色体接触频率,研究人员大大提高了全基因组结构建模的准确性。最后,研究人员绘制了DNA双链断裂、生殖系变异和癌症突变的放射状拓扑图谱,并发现它们在A和B亚区室中具有独特的放射状排列。研究人员认为,GPSeq可以揭示基因组结构的基本信息。

据悉,除了与核纤层相关的结构域外,哺乳动物细胞中染色质的放射状组织在很大程度上仍未知。

附:英文原文

Title: GPSeq reveals the radial organization of chromatin in the cell nucleus

Author: Gabriele Girelli, Joaquin Custodio, Tomasz Kallas, Federico Agostini, Erik Wernersson, Bastiaan Spanjaard, Ana Mota, Solrun Kolbeinsdottir, Eleni Gelali, Nicola Crosetto, Magda Bienko

Issue&Volume: 2020-05-25

Abstract: With the exception of lamina-associated domains, the radial organization of chromatin in mammalian cells remains largely unexplored. Here we describe genomic loci positioning by sequencing (GPSeq), a genome-wide method for inferring distances to the nuclear lamina all along the nuclear radius. GPSeq relies on gradual restriction digestion of chromatin from the nuclear lamina toward the nucleus center, followed by sequencing of the generated cut sites. Using GPSeq, we mapped the radial organization of the human genome at 100-kb resolution, which revealed radial patterns of genomic and epigenomic features and gene expression, as well as A and B subcompartments. By combining radial information with chromosome contact frequencies measured by Hi-C, we substantially improved the accuracy of whole-genome structure modeling. Finally, we charted the radial topography of DNA double-strand breaks, germline variants and cancer mutations and found that they have distinctive radial arrangements in A and B subcompartments. We conclude that GPSeq can reveal fundamental aspects of genome architecture.

DOI: 10.1038/s41587-020-0519-y

Source: https://www.nature.com/articles/s41587-020-0519-y

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex