Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence (DamID-seq)

ABSTRACT: Background. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene. Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL. Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76594 | GEO | 2017/08/17

SECONDARY ACCESSION(S): PRJNA308127

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence (RNA-seq)

Project description:Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene. Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL. Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.

2017-08-17 | GSE75643 | GEO

Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence (genome tiling)

Project description:Background. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene. Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL. Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.

2017-08-17 | GSE76646 | GEO

Redistribution of the Lamin B1 genomic binding profile affects spatial rearrangement of heterochromatic domains and gene expression during senescence

Project description:Senescence is a stress responsive form of stable cell cycle exit. Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Studying a key component of the nuclear lamina, lamin B1 (LMNB1), we report dynamic alterations in its genomic profile and their implications for SAHF formation and gene regulation during senescence. Genome-wide mapping reveals that LMNB1 is depleted during senescence, preferentially from the central regions of lamina-associated domains (LADs), which are enriched for H3K9me3. LMNB1 knockdown facilitates the spatial relocalization of perinuclear H3K9me3, thus promoting SAHF formation, which is inhibited by ectopic LMNB1 expression. Furthermore, despite the global reduction in LMNB1 protein levels, LMNB1 binding increases during senescence in a small subset of gene-rich regions where H3K27me3 also increases and gene expression becomes repressed. These results suggest that LMNB1 may contribute to senescence in at least two ways due to its uneven genomewide redistribution: firstly through the spatial re-organization of chromatin and, secondly, through gene repression. ChIP-seq for Lamin B1 in Growing and Ras Induced Senescence

2013-08-22 | E-GEOD-49341 | biostudies-arrayexpress

Genome-wide maps of nuclear lamina interactions in single human cells. (Hi-C, KBM7 haploid)

Project description:Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of ~400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts are more sensitive to a change in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, single-cell gene expression and chromatin accessibility analysis shows that loci with consistent NL contacts are expressed at lower levels and are more consistently inaccessible than loci with lower contact frequencies. These results highlight fundamental principles of single cell chromatin organization. Hi-C Data

2015-09-24 | E-GEOD-69841 | biostudies-arrayexpress

Genome-wide maps of nuclear lamina interactions in single human cells (CEL-seq)

2015-09-24 | E-GEOD-68596 | biostudies-arrayexpress

DNMT1 drives 4D genome rewiring during oncogene induced senescence

Project description:While, transcriptional and epigenetic changes associated senescence processes are well studied, the 3D chromatin changes associated with it remains elusive. In this study, we have generated genome wide chromatin interaction maps (Hi-C), epigenetic (ChIP-Seq), replication-timing and gene expression (RNA-Seq) profiles from replication induced (RS) and oncogene induced (OIS) senescent cells. As senescence associated heterochromatin foci (SAHFs) differentiates both RS and OIS nuclei, we identified the regions that constitute SAHFs and called them Senescence Associated Heterochromatin Domains (SAHDs). Further, screening of candidate factors for SAHF induction allowed us to identify DNMT1 as a novel component that induces SAHFs by stimulation of HMGA2 expression. DNMT1 depletion does not reverse the senescence process, however, instead, depleted cells transition to a 3D genome conformation akin to that of cells in replicative senescence, suggesting that acute senescence induction (OIS) involves SAHF formation in addition to the RS-dependent 3D genome rewiring.

2020-03-27 | GSE130306 | GEO

Redistribution of the Lamin B1 genomic binding profile affects spatial rearrangement of heterochromatic domains and gene expression during senescence

2013-08-22 | GSE49341 | GEO

The insulator protein SU(HW) modulates nuclear lamina interactions of the Drosophila genome: expression

Project description:Specific interactions of the genome with the nuclear lamina (NL) are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs) in the human genome, and suggested that the insulator protein CTCF may help to demarcate these domains. Here, we report the detailed structure of LADs in Drosophila cells, and investigate the putative roles of five insulator proteins in LAD organization. We found that of these five proteins, only SU(HW) binds preferentially at LAD borders and at specific positions inside LADs, while GAF, CTCF, BEAF-32 and DWG are mostly absent from these regions. By knockdown and overexpression studies we demonstrate that SU(HW) weakens LAD M-bM-^@M-^S NL interactions by a local antagonistic effect. Our results provide insights into the evolution of LAD organization and reveal a role for SU(HW) in the regulation of genome M-bM-^@M-^S NL interactions. RNA was isolated from three independent Drosophila Kc167 cell cultures. Expression profiles were made of self-self hybridizations on spotted INDAC long oligo arrays. The three replicates were averaged.

2011-01-24 | E-GEOD-20312 | biostudies-arrayexpress

Genome-wide maps of nuclear lamina interactions in single human cells (CEL-seq)

2015-09-24 | GSE68596 | GEO