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Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus

ABSTRACT: Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus

PROVIDER: PRJNA472993 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7216000_1.fastq.gz	Fastqsanger.gz
	SRR7216000_2.fastq.gz	Fastqsanger.gz
	SRR7216010_1.fastq.gz	Fastqsanger.gz
	SRR7216010_2.fastq.gz	Fastqsanger.gz
	SRR7216001_1.fastq.gz	Fastqsanger.gz

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Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus

Project description:We develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which enables genome-wide detection of higher-order interactions that occur simultaneously within the nucleus in a proximity-ligation independent manner. We generated SPRITE maps in two mammalian cell types – mouse embryonic stem cells (mES) and human lymphoblastoid cells (GM12878). We generated ~1.5 billion sequencing reads from each sample and recapitulate known genome structures identified by Hi-C, including chromosome territories, compartments, topologically associated domains, and loop structures, and identify that many of these occur within higher-order structures in the nucleus. Because SPRITE does not rely on proximity-ligation, we find that SPRITE identifies interactions that occur across larger spatial distances than can be observed by Hi-C. These long-range interactions include two major hubs of inter-chromosomal interactions. We extended SPRITE to enable simultaneous measurements of RNA and DNA interactions and observe ribosomal RNA interactions across specific regions on the genome that correspond to DNA organization around the nucleolus. We show that gene-dense regions that are highly transcribed by PolII organize around nuclear speckles and gene poor, and therefore transcriptionally inactive, regions that are centromere-proximal organize around the nucleolus. In addition to the regions that directly associate around these nuclear bodies, we find that a substantial fraction of the genome exhibits preferential spatial positioning in the nucleus relative to each of these nuclear bodies and that the spatial preferences identified by SPRITE are highly correlated with 3D distances measured by microscopy.

2018-06-07 | GSE114242 | GEO

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

Project description: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.

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