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Nuclear speckles as a key regulator for the 3D genome organization [RNA-Seq]

ABSTRACT: Nuclear speckles as a key regulator for the 3D genome organization [RNA-Seq]

PROVIDER: PRJNA541491 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9023031_1.fastq.gz	Fastqsanger.gz
	SRR9023031_2.fastq.gz	Fastqsanger.gz
	SRR9023032_1.fastq.gz	Fastqsanger.gz
	SRR9023032_2.fastq.gz	Fastqsanger.gz
	SRR9023033_1.fastq.gz	Fastqsanger.gz

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Nuclear speckles as a key regulator for the 3D genome organization

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Genome organization around nuclear speckles drives mRNA splicing efficiency

Project description:The nucleus is highly organized such that factors involved in transcription and processing of distinct classes of RNA are organized within specific nuclear bodies. One example is the nuclear speckle, which is defined by high concentrations of protein and non-coding RNA regulators of pre-mRNA splicing. What functional role, if any, speckles might play in the process of mRNA splicing remains unknown. Here we show that genes localized near nuclear speckles display higher spliceosome concentrations, increased spliceosome binding to their pre-mRNAs, and higher co-transcriptional splicing levels relative to genes that are located farther from nuclear speckles. We show that directed recruitment of a pre-mRNA to nuclear speckles is sufficient to increase mRNA splicing levels. Finally, we show that gene organization around nuclear speckles is highly dynamic with differential localization between cell types corresponding to differences in splicing efficiency. Together, our results integrate the longstanding observations of nuclear speckles with the biochemistry of mRNA splicing and demonstrate a critical role for dynamic 3D spatial organization of genomic DNA in driving spliceosome concentrations and controlling the efficiency of mRNA splicing.

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Nuclear speckles as a key regulator for the 3D genome organization [HiC]

Project description:The nuclei of eukaryotes contain various higher-order chromatin architectures and nuclear bodies (NBs), which are critical for proper nuclear functions. By using mouse hepatocytes as the model, we knocked-down SRRM2, a core protein component scaffolding NSs, and performed Hi-C experiments to examine genome-wide chromatin interactions. We found that Srrm2 depletion disrupted the NSs and changes expression of about 1,000 genes. The intra-chromosomal interactions were decreased in type A (active) compartments and increased in type B (repressive) compartments. Furthermore, upon Srrm2 knockdown, the insulation of TADs was decreased specifically in active compartments, and the most significant reduction was found in the A1 sub-compartments. We showed that disruption of NSs by Srrm2 knockdown led to a global decrease of chromatin interactions in active compartments, indicating critical functions of NSs in the organization of the 3D genome.

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Nuclear speckles as a key regulator for the 3D genome organization [RNA-Seq]

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Nuclear speckles as a key regulator for the 3D genome organization

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Genome organization around nuclear speckles drives mRNA splicing efficiency

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The nuclear matrix associating protein HNRNPU functions as a key regulator of 3D genome architecture [ChIP-Seq 2]

Project description:Here we show that HNRNPU, the major nuclear matrix attachment factor, is necessary to maintain proper nuclear architecture in mouse hepatocytes. Upon HNRNPU depletion, the interactions between chromatin and nuclear lamina have been changed dramatically；chromatin organization is globally changed; boundaries of topologically associating domains (TADs) become weaker; inter-TAD interactions are increased; thousands of genes are significantly altered coincident with 3D chromatin changes. Mechanically, HNRNPU interacts with CTCF and RAD21, which affects the binding of RAD21 to the chromatin significantly, whereas CTCF bindings are almost unchanged, what’ more, the decrease of binding strengths are highly correlated with the weakness of loop bounded by Rad21. Taken together, we identify HNRNPU as a key regulator of chromatin architecture, and our data suggest the importance of nuclear matrix associating factors in 3D genome organization.

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