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

Quinodoz, Sofia A. and Ollikainen, Noah and Tabak, Barbara and Palla, Ali and Schmidt, Jan Marten and Detmar, Elizabeth and Lai, Mason M. and Shishkin, Alexander A. and Bhat, Prashant and Takei, Yodai and Trinh, Vickie and Aznauryan, Erik and Russell, Pamela and Cheng, Christine and Jovanovic, Marko and Chow, Amy and Cai, Long and McDonel, Patrick and Garber, Manuel and Guttman, Mitchell (2018) Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus. Cell, 174 (3). pp. 744-757. ISSN 0092-8674. PMCID PMC6548320. doi:10.1016/j.cell.2018.05.024.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle Paper
Quinodoz, Sofia A.0000-0003-1862-5204
Ollikainen, Noah0000-0002-1174-2400
Bhat, Prashant0000-0003-3832-4871
Takei, Yodai0000-0002-7226-5185
Cai, Long0000-0002-7154-5361
Garber, Manuel0000-0001-8732-1293
Guttman, Mitchell0000-0003-4748-9352
Alternate Title:Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus
Additional Information:© 2018 Elsevier Inc. Received 14 November 2017, Revised 18 March 2018, Accepted 10 May 2018, Available online 7 June 2018, Published: June 7, 2018. We thank F. Alber, J. Jachowicz, A. Lin, K. Plath, J. Rinn, M. Thomson, W.G. Walkup, and B. Wold for manuscript comments; S. Knemeyer for illustrations; and B. Belin for naming SPRITE. Imaging was performed in the Biological Imaging Facility, with advice from A. Collazo and S. Wilbert. Sequencing was performed at the Millard and Muriel Jacobs Genetics and Genomics Laboratory with assistance from I. Antoshechkin. S.A.Q. was funded by a HHMI Gilliam Fellowship and NSF GRFP Fellowship. P.B. was funded by NIGMS (T32 GM008042) and UCLA-Caltech MSTP (NIGMS T32 GM008042). This work was funded by the NIH 4DN Program (U01 DA040612 and U01 HL130007), NHGRI GGR Program (U01 HG007910), New York Stem Cell Foundation (NYSCF-R-I13), Sontag Foundation, and funds from Caltech. M. Guttman is a NYSCF-Robertson Investigator. Author Contributions: Conceptualization, S.A.Q., C.C., M.J., and M. Guttman; Methodology, S.A.Q., N.O., B.T., J.M.S., A.A.S., A.C., Y.T., P.M., M. Garber, and M. Guttman; Software, N.O., B.T., M.M.L., P.R., and M. Guttman; Validation, S.A.Q., A.P., and Y.T.; Formal Analysis, S.A.Q., N.O., B.T., A.P., M.L., M. Garber, and M. Guttman; Investigation, S.A.Q., A.P., J.M.S., E.D., A.A.S., P.B., V.T., E.A., A.C., and Y.T.; Resources, L.C., M. Garber, and M. Guttman; Data Curation, S.A.Q., N.O., M.L., B.T., and M. Guttman; Writing, S.A.Q., N.O., and M. Guttman; Supervision, S.A.Q., M. Garber, and M. Guttman; and Funding Acquisition, M. Guttman. Declaration of Interests: S.A.Q. and M.G. are inventors on a provisional patent on the SPRITE method.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
NIH Predoctoral FellowshipT32 GM008042
NIHU01 DA040612
NIHU01 HL130007
NIHU01 HG007910
New York Stem Cell FoundationNYSCF-R-I13
Sontag FoundationUNSPECIFIED
Subject Keywords:Nuclear structure; nuclear organization; genome structure; nuclear speckle; nucleolus; SPRITE; RNA DNA interactions; higher-order nuclear structure; multi-way interactions
Issue or Number:3
PubMed Central ID:PMC6548320
Record Number:CaltechAUTHORS:20180607-101054915
Persistent URL:
Official Citation:Sofia A. Quinodoz, Noah Ollikainen, Barbara Tabak, Ali Palla, Jan Marten Schmidt, Elizabeth Detmar, Mason M. Lai, Alexander A. Shishkin, Prashant Bhat, Yodai Takei, Vickie Trinh, Erik Aznauryan, Pamela Russell, Christine Cheng, Marko Jovanovic, Amy Chow, Long Cai, Patrick McDonel, Manuel Garber, Mitchell Guttman, Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus, Cell, Volume 174, Issue 3, 2018, Pages 744-757.e24, ISSN 0092-8674, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86878
Deposited By: Tony Diaz
Deposited On:07 Jun 2018 18:33
Last Modified:01 Jun 2023 22:37

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