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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]

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

PROVIDER: PRJNA736446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14768747_1.fastq.gz	Fastqsanger.gz
	SRR14768747_2.fastq.gz	Fastqsanger.gz

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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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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 [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 [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.

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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]

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

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

2021-08-25 | GSE176503 | 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.

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