FUS facilitates gene body export from nuclear condensates
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233266 | GEO | 2023/05/30
REPOSITORIES: GEO
Similar Datasets
Project description:FUS facilitates gene body export from nuclear condensates
| PRJNA975594 | ENA
Project description:Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV de-repression is associated with lethality during early development has been a mystery. Here we report that rapid and selective degradation of the TRIM28 heterochromatin adapter protein triggers dissociation of transcriptional condensates from loci encoding super-enhancer -driven pluripotency genes, and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of super-enhancer -enriched transcription factors rescued condensate localization at super-enhancers in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA Polymerase II, and the Mediator co- activator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-Seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and non-coding nascent RNAs, including those produced by retrotransposons, may facilitate “hijacking” of transcriptional condensates in various developmental and disease contexts.
2022-03-30 | GSE159468 | GEO
Project description:While eukaryotic cells have a myriad of membrane-bound organelles enabling the isolation of different chemical environments, prokaryotic cells lack these defined reaction vessels. Biomolecular condensates—organelles that lack a membrane—provide a strategy for cellular organization without a physical barrier while allowing for the dynamic, responsive organization of the cell. It is well established that intrinsically disordered protein domains drive condensate formation via liquid–liquid phase separation; however, the role of globular protein domains on intracellular phase separation remains poorly understood. We hypothesized that the overall charge of globular proteins would dictate the formation and concentration of condensates and systematically probed this hypothesis with supercharged proteins and nucleic acids in E. coli. Within this study, we demonstrated that condensates form via electrostatic interactions between engineered proteins and RNA and that these condensates are dynamic and only enrich specific nucleic acid and protein components. Herein, we propose a simple model for the phase separation based on protein charge that can be used to predict intracellular condensate formation. With these guidelines, we have paved the way to designer functional synthetic membraneless organelles with tunable control over globular protein function.
2020-04-24 | MSV000085333 | MassIVE
Project description:The gene expression programs that define each cell’s identity are controlled by master transcription factors (TFs) that bind cell-type specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here we present evidence that signaling factors for the WNT, TGF-β and JAK/STAT pathways employ their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA binding factors to selectively occupy super-enhancer associated genes. We propose that the cell-type specificity of the response to signaling is mediated, in part, by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity.
2020-01-31 | GSE134387 | GEO
Project description:Insulin resistance is accompanied by chronic hyperinsulinemia and is associated with type 2 diabetes and other metabolic syndromes in a substantial portion of the population. The risk factors and features of insulin resistance have been thoroughly described but its mechanistic triggers are still under study. Here we consider a condensate model for insulin receptor (IR) function in normal conditions and when dysregulated in chronic hyperinsulinemia-induced insulin resistance. We find that IR is incorporated into liquid-like condensates at the plasma membrane, in the cytoplasm and in the nucleus of liver cells, and provide evidence for insulin-dependent IR function in condensates. Insulin stimulation promotes further incorporation of IR into these dynamic condensates in insulin sensitive cells, which form and dissolve on short, sub-minute time-scales. In contrast, insulin stimulation does not promote further incorporation of IR into condensates in insulin resistant cells, where IR molecules within condensates exhibit less dynamic behavior. Metformin treatment of insulin resistant cells rescues IR condensate dynamics and insulin responsiveness. Insulin resistant cells experience high levels of oxidative stress, which causes reduced condensate dynamics, and treatment of these cells with metformin reduces ROS levels and returns condensates to their normal dynamic behavior. The condensate model we propose can account for features of normal and dysregulated insulin response and has implications for improved therapeutic approaches to insulin resistance.
2023-07-28 | GSE181096 | GEO
Project description:Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis, does not involve other known selective autophagy receptors, but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates – at the plasma membrane and in autophagic bodies – shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy pathway. Our results imply an important role of autophagy in surveillance of membraneless compartments
2020-11-23 | PXD019083 | Pride
Project description:Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. We here report a multi-layered mechanism for condensate assembly by Autoimmune regulator (Aire), an essential transcriptional regulator (TR) that orchestrates gene expression reprogramming for central T-cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain CARD, histone binding domain PHD1 and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of TRs.
2024-07-08 | GSE243823 | GEO
Project description:Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. We here report a multi-layered mechanism for condensate assembly by Autoimmune regulator (Aire), an essential transcriptional regulator (TR) that orchestrates gene expression reprogramming for central T-cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain CARD, histone binding domain PHD1 and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of TRs. This SuperSeries is composed of the SubSeries listed below.
2024-07-08 | GSE243825 | GEO
Project description:Nine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours. Experiment Overall Design: Primary human bronchial/tracheal epithelial cells were grown in culture and treated with 10 different sources of cigarette smoke condensates.
2009-10-03 | E-GEOD-18235 | biostudies-arrayexpress
Project description:MeCP2 (methyl CpG binding protein 2) is a key component of constitutive heterochromatin, which plays important roles in chromosome maintenance and transcriptional silencing. Mutations in MeCP2 cause Rett syndrome (RTT), a postnatal progressive neurodevelopmental disorder associated with severe mental disability and autism-like symptoms that manifests in girls during early childhood. Heterochromatin, long considered a dense and relatively static structure, is now understood to exhibit properties consistent with a liquid-like condensate. Here we report that MeCP2 is a dynamic component of heterochromatin condensates in cells, is stimulated by DNA to form liquid-like condensates, contains multiple domains that contribute to condensate formation, manifests physicochemical properties that selectively concentrate heterochromatin cofactors compared to components of transcriptionally active condensates, and when altered by RTT-causing mutations is disrupted in its ability to form condensates. We propose that MeCP2 enhances heterochromatin/euchromatin separation through its condensate partitioning properties and that condensate disruption may be a common consequence of RTT patient mutations.
2020-06-23 | GSE139033 | GEO