新技術揭示細胞核染色質的放射狀結構
作者：
小柯機器人發布時間：2020/5/28 12:59:45
瑞典卡羅林斯卡學院Magda Bienko、Nicola Crosetto等研究人員合作利用GPSeq技術來揭示了細胞核中染色質的放射狀結構。這一研究成果於2020年5月25日在線發表在《自然—生物技術》上。
研究人員報導了通過測序進行基因座定位的方法（GPSeq），這是一種全基因組方法，可推斷整個核半徑上與核纖層的距離。GPSeq依賴於從核纖層到核中心的染色質逐步限制性消化，然後對產生的切割位點進行測序。使用GPSeq，研究人員以100 kb的解析度繪製了人類基因組的徑向組織圖譜，從而揭示了基因組和表觀基因組特徵與基因表達以及A和B亞區室的徑向模式。
通過結合徑向信息和Hi-C測量的染色體接觸頻率，研究人員大大提高了全基因組結構建模的準確性。最後，研究人員繪製了DNA雙鏈斷裂、生殖系變異和癌症突變的放射狀拓撲圖譜，並發現它們在A和B亞區室中具有獨特的放射狀排列。研究人員認為，GPSeq可以揭示基因組結構的基本信息。
據悉，除了與核纖層相關的結構域外，哺乳動物細胞中染色質的放射狀組織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