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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176503 | GEO | 2021/08/25

REPOSITORIES: GEO

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Noncoding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability.

Project description:Most noncoding regions of the human genome do not harbor any annotated element and are even not marked with any epigenomic or protein binding signal. However, an overlooked aspect of their possible role in stabilizing 3D chromatin organization has not been extensively studied. To illuminate their structural importance, we started with the noncoding regions forming many 3D contacts (referred to as hubs) and performed a CRISPR library screening to identify dozens of hubs essential for cell viability. Hi-C and single-cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and affect the expressions of distal genes. This study revealed the 3D structural importance of noncoding loci that are not associated with any functional element, providing a previously unknown mechanistic understanding of disease-associated genetic variations (GVs). Furthermore, our analyses also suggest a possible approach to develop therapeutics targeting disease-specific noncoding regions that are critical for disease cell survival.

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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [HiC]

Project description:Most non-coding regions of the human genome do not harbour any annotated element and are even not marked with any epigenomic or protein binding signal. However, an overlooked aspect of their possible role in stabilizing 3D chromatin organization has not been extensively studied. To illuminate their structural importance, we started with the non-coding regions forming many 3D contacts (referred to as hubs) and performed a CRISPR library screening to identify dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact the distal genes expression. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of disease-associated genetic variations (GVs), and we focused on single nucleotide variations. Furthermore, our analyses also suggest a powerful approach to develop "one-drug-multiple-targets" therapeutics targeting disease-specific non-coding regions.

2021-08-25 | GSE176500 | GEO

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [bulk RNA-seq]

Project description:In this study, we performed network analysis on Hi-C data and identified a group of non-coding regions forming many 3D contacts (referred to as hubs). Through a high-throughput CRISPR-Cas9 library screening by targeted deletion, we discovered that some hubs without any epigenetic marks were essential for cell growth and survival. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact the distal genes expression. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of disease-associated genetic variations. Furthermore, our analyses also suggest a powerful approach to develop "one-drug-multiple-targets" therapeutics targeting disease-specific non-coding regions.

2021-08-25 | GSE176501 | GEO

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [single-cell RNA-seq]

2021-08-25 | GSE176502 | GEO

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

Project description:Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [HiC]

Project description:Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [HiC]

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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [bulk RNA-seq]

Project description:Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [bulk RNA-seq]

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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [single-cell RNA-seq]

Project description:Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [single-cell RNA-seq]

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Regulatory elements can be essential for maintaining broad chromatin organization and cell viability.

Project description:Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for their roles in forming canonical chromatin loops, promoters and enhancers have not been well studied regarding the maintenance of broad chromatin organization. Here, we focused on the active promoters/enhancers predicted to form many 3D contacts with other active promoters/enhancers (referred to as hotspots) and identified dozens of loci essential for cell growth and survival through CRISPR screening. We found that the deletion of an essential hotspot could lead to changes in broad chromatin organization and the expression of distal genes. We showed that the essentiality of hotspots does not result from their association with individual genes that are essential for cell viability but rather from their association with multiple dysregulated non-essential genes to synergistically impact cell fitness.

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Myosin Va plays essential roles in maintaining normal mitosis, enhancing tumor cell motility and viability.

Project description:Myosin Va, a member of Class V myosin, functions in organelle motility, spindle formation, nuclear morphogenesis and cell motility. The purpose of this study is to explore the expression and localization of myosin Va in testicular cancer and prostate cancer, and its specific roles in tumor progression including cell division, migration and proliferation. We detected myosin Va in testicular and prostate tumor tissues using sqRT-PCR, western blot, and immunofluorescence. Tumor samples showed an increased expression of myosin Va, abnormal actin and myosin Va distribution. Immunofluorescence images during the cell cycle showed that myosin Va tended to gather at cytoplasm during anaphase but co-localized with nucleus during other phases, suggesting the roles of myosin Va in disassembly of spindle microtubule, movement of chromosomes and normal cytokinesis. In addition, multi-nucleation and aberrant nuclear morphology were observed in myosin Va-knockdown cells. Wounding assay and CCK-8-based cell counting were conducted to explore myosin Va roles in cell migration, viability and proliferation. Our results suggest that myosin Va plays essential roles in maintaining normal mitosis, enhancing tumor cell motility and viability, and these properties are the hallmark of tumor progression and metastasis development. Therefore, an increased understanding of myosin Va expression and function will assist in the development of future oncodiagnosis and -therapy.

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