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

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

PROVIDER: PRJNA736444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14768742_1.fastq.gz	Fastqsanger.gz
	SRR14768742_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

| PRJNA736443 | ENA

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

| PRJNA736445 | ENA

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]

| PRJNA736446 | ENA

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.

| S-EPMC8565911 | biostudies-literature

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: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.

2021-08-25 | GSE176501 | GEO

C42B HiC

Project description:C42B HiC

| PRJNA843050 | ENA

Selective enhancement and repression of glucocorticoid receptor signaling by coregulator Hic-5

Project description:The glucocorticoid receptor (GR) recruits many coregulators via the well characterized AF2 interaction surface in the GR ligand binding domain, but LIM domain coregulator Hic-5 binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of Hic-5 for glucocorticoid-regulated gene expression in U2OS osteosarcoma cells was defined by Hic-5 depletion and global gene expression analysis. Hic-5 depletion had selective and dramatic effects, positive and negative, on both activation and repression of GR target genes. For some hormone-induced genes, Hic-5 facilitated recruitment of the Mediator complex and RNA polymerase II. In contrast, many genes were not regulated by hormone until Hic-5 was depleted. On these genes Hic-5 acted at a very early step of the regulatory process, preventing efficient GR binding on enhancers, chromatin remodeling, and thus preventing glucocorticoid-driven transcriptional regulation. Overall, Hic-5 has selective and diverse roles on GR target genes, functioning as coactivator on some genes and corepressor on others, and either facilitating or opposing the glucocorticoid-driven actions of GR. Hic-5 exhibits multiple mechanisms of action, either regulating GR binding to DNA and chromatin remodeling, or facilitating later steps in transcription complex assembly. We investigate the relationship between GR and Hic5 and identify classes of genes that respond differently when cells are induced with hormone and when Hic5 is knocked down We knock down Hic-5 (TGFB1I1) in U2OS cells using siRNA (siHic5_2) along with nonspecific siRNA (shNS) and assay gene expression changes at 4 different time points of hormone treatment. We also include non-infected control (NI) as a second control at each time point.

2014-03-21 | E-GEOD-46448 | biostudies-arrayexpress

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