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

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus.
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DOI:
10.1016/j.cell.2018.05.024
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发表时间:
2018-07-26
期刊:
影响因子:
64.5
通讯作者:
Guttman M
Guttman M
中科院分区:
生物学1区
文献类型:
--
作者:
Quinodoz SA;Ollikainen N;Tabak B;Palla A;Schmidt JM;Detmar E;Lai MM;Shishkin AA;Bhat P;Takei Y;Trinh V;Aznauryan E;Russell P;Cheng C;Jovanovic M;Chow A;Cai L;McDonel P;Garber M;Guttman M

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Eukaryotic genomes are packaged into a three-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 to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which 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. IN BRIEF: SPRITE is introduced as a method that enables genome-wide detection of multiple simultaneously occurring higher-order DNA interactions within the nucleus and provides a global picture of interchromosomal spatial arrangement around nuclear bodies
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