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

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

PROVIDER: PRJNA543769 | 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 [HiC]

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

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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 [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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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 [RNA-Seq]

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-06-30 | GSE131466 | GEO

B-Type Lamins organize 3D chromatin architecture through associations with nuclear lamina and nuclear speckles [TSA]

Project description:B-type lamins (Lamin B1 and B2) are key components of the nuclear lamina and play essential roles in three-dimensional (3D) chromatin organization by anchoring Lamina-Associated Domains (LADs). Recent studies have indicated that abnormal gene expression resulting from B-type lamin loss occurs in both LAD and non-LAD regions; however, the underlying molecular mechanisms remain unclear. In this study, we demonstrate that the majority of differentially expressed genes (DEGs) in B-type lamin-depleted cells are predominantly located in non-LAD regions, which are characterized by a constitutive association with nuclear speckles. Through RNA-Seq combined with SC35 Tyramide Signal Amplification Sequencing (TSA-Seq) analysis, we find that aberrant gene regulation is closely associated with the repositioning of chromatin either toward or away from nuclear speckles. The absence of B-type lamins causes a global reorganization of chromatin rather than changes in its fine structure, leading to the disruption of constitutive Speckle-Associated Domains (cSPADs). Additionally, the loss of B-type lamins results in euchromatin deactivation and heterochromatin de-repression, which impairs cell viability by increasing apoptotic signaling and causes defective mRNA splicing. Our data reveal a novel role for B-type lamins in regulating transcriptional activity by conserving genome architecture between the nuclear lamina and nuclear speckles.

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B-Type Lamins organize 3D chromatin architecture through associations with nuclear lamina and nuclear speckles [RNA-seq]

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