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Cell. 2018 Jul 26;174(3):744-757.e24. doi: 10.1016/j.cell.2018.05.024. Epub 2018 Jun 7.

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus.

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
2
Program in Bioinformatics and Integrative Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
3
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
5
Department of Biology, Boston University, Boston, MA 02215, USA.
6
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
7
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: mguttman@caltech.edu.

Abstract

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.

KEYWORDS:

Nuclear structure; RNA DNA interactions; SPRITE; genome structure; higher-order nuclear structure; multi-way interactions; nuclear organization; nuclear speckle; nucleolus

PMID:
29887377
DOI:
10.1016/j.cell.2018.05.024

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