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GPSeq reveals the radial organization of chromatin in the cell nucleus

Item Type:Article
Title:GPSeq reveals the radial organization of chromatin in the cell nucleus
Creators Name:Girelli, G. and Custodio, J. and Kallas, T. and Agostini, F. and Wernersson, E. and Spanjaard, B. and Mota, A. and Kolbeinsdottir, S. and Gelali, E. and Crosetto, N. and Bienko, M.
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.
Keywords:Cell Nucleus, Chromatin, Epigenomics, Gene Expression Regulation, Human Genome, High-Throughput Nucleotide Sequencing
Source:Nature Biotechnology
Publisher:Nature Publishing Group
Page Range:1184-1193
Date:October 2020
Additional Information:Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright notice: Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
Official Publication:https://doi.org/10.1038/s41587-020-0519-y
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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