Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA336027 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cellular senescence is a stable cell growth arrest that is characterized by silencing of proliferation-promoting genes through compaction of individual chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased expression of certain secreted factors such as cytokines and chemokines, known as senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear. Here we report that HMGB2 orchestrates the chromatin landscape of SASP gene loci. HMGB2 preferentially localizes to SASP gene loci during senescence. Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlated with incorporation of SASP gene loci into SAHF. Our results establish HMGB2 as a novel master regulator that orchestrates SASP through preventing heterochromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment during senescence.
2016-10-11 | GSE85057 | GEO
Project description:Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications and other chromatin features at pathology-associated genes. It remains unknown the extent to which genome-wide chromatin reorganization also contributes to the pathologic gene expression. We examined the roles of two chromatin structural proteins, CTCF (CCCTC-binding factor) and HMGB2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling. Our data demonstrate a reciprocal relationship between HMGB2 and CTCF in controlling aspects of chromatin structure and gene expression. Both proteins regulate each otherâs expression as well as transcription in cardiac myocytes: however, only HMGB2 does so in a manner that involves global reprogramming of chromatin accessibility. We demonstrate that the actions of HMGB2 on local chromatin accessibility are conserved across genomic loci, whereas the effects on transcription are loci-dependent and emerge in concert with histone modification and other chromatin features. Lastly, while both proteins share gene targets, HMGB2 and CTCF neither bind these genes simultaneously nor do they physically co-localize in myocyte nuclei. Our study uncovers a previously unknown relationship between these two ubiquitous chromatin proteins and provides a mechanistic explanation for how HMGB2 regulates gene expression and cellular phenotype. Furthermore, we demonstrate direct evidence for hierarchical remodeling of chromatin on a genome-wide scale in the setting of cardiac disease. Examination of a chromatin structural protein, HMGB2 in basal and agonist-treated cells.
2016-06-15 | E-GEOD-80453 | biostudies-arrayexpress
Project description:Pericentromeric noncoding RNA drives the senescence-associated secretory phenotype
| PRJDB10513 | ENA
Project description:Pericentromeric noncoding RNA drives the senescence-associated secretory phenotype
| PRJDB9443 | ENA
Project description:ADAM19 Mediates Cellular Senescence and the Senescence-Associated Secretory Phenotype
2020-04-03 | MSV000085224 | MassIVE
Project description:Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications and other chromatin features at pathology-associated genes. It remains unknown the extent to which genome-wide chromatin reorganization also contributes to the pathologic gene expression. We examined the roles of two chromatin structural proteins, CTCF (CCCTC-binding factor) and HMGB2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling. Our data demonstrate a reciprocal relationship between HMGB2 and CTCF in controlling aspects of chromatin structure and gene expression. Both proteins regulate each other’s expression as well as transcription in cardiac myocytes: however, only HMGB2 does so in a manner that involves global reprogramming of chromatin accessibility. We demonstrate that the actions of HMGB2 on local chromatin accessibility are conserved across genomic loci, whereas the effects on transcription are loci-dependent and emerge in concert with histone modification and other chromatin features. Lastly, while both proteins share gene targets, HMGB2 and CTCF neither bind these genes simultaneously nor do they physically co-localize in myocyte nuclei. Our study uncovers a previously unknown relationship between these two ubiquitous chromatin proteins and provides a mechanistic explanation for how HMGB2 regulates gene expression and cellular phenotype. Furthermore, we demonstrate direct evidence for hierarchical remodeling of chromatin on a genome-wide scale in the setting of cardiac disease.
2016-06-15 | GSE80453 | GEO
Project description:MLL1 is essential for the senescence-associated secretory phenotype [RNA-Seq]
| PRJNA312767 | ENA
Project description:MLL1 is essential for the senescence-associated secretory phenotype [ChIP-Seq]
| PRJNA312768 | ENA
Project description:Cellular senescence is a homeostatic program associated with tumor suppression, wound healing, and certain age related pathologies. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes, while at the same time activate an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program.
2016-04-15 | GSE74324 | GEO
Project description:Cellular senescence is a homeostatic program associated with tumor suppression, wound healing, and certain age related pathologies. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes, while at the same time activate an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program.
2016-04-15 | GSE74238 | GEO