Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA933137 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Polycomb-repressive complex 1 (PRC1) has a constraining influence on 3D genome organization, mediating localized and chromosome-wide clustering of target loci. Polycomb-bound regions form transcriptionally repressive chromatin domains independent of topologically associating domains (TADs). Several subunits of PRC1 have the capacity to form biomolecular condensates through liquid-liquid phase separation (LLPS) in vitro and when tagged and over-expressed in cells. Here, we use 1,6 hexandiol (1,6-HD), which disrupts liquid-like condensates, to examine the role of endogenous PRC1 biomolecular condensates on local and chromosome-wide clustering of PRC1-bound loci. Using imaging and chromatin immunoprecipitation combined with deep sequencing (ChIP-seq) analyses, we show that PRC1-mediated localized chromatin compaction and clustering of targeted genomic loci at megabase and tens of megabase scales can be reversibly disrupted by the addition and subsequent removal of 1,6-HD to mouse embryonic stem cells (mESCs). Decompaction and dispersal of polycomb domains and clusters cannot be solely attributable to the reduction of PRC1 binding following 1,6-HD treatment as the addition of 2,5-HD has similar effects despite this alcohol not perturbing PRC1-mediated clustering, at least at the sub-megabase and megabase scales. These results suggest that weak, hydrophobic interactions between PRC1 molecules characteristic of liquid condensates do have a role in polycomb-mediated genome organization.
2023-02-13 | GSE224930 | GEO
Project description:R-loops are three-stranded nucleic acid structures that form naturally during transcription, especially over unmethylated CpG-rich promoters. In mESC, such promoters of developmental regulator genes are occupied by the Polycomb-repressor complexes PRC1 and PRC2. Here we have explored the possibility that R-loops form over Polycomb-repressed genes and play a role in their transcriptional silencing. Using single gene and genome-wide analyses, we show that R-loops form at a specific subset of PRC-target genes and contribute to Polycomb occupancy on chromatin. Removal of R-loops leads to an up-regulation of nascent and processed transcripts and the appearance of the elongating form of RNA polymerase II. In contrast, removal of PRC2 does not influence R-loop formation, transcriptional repression and PRC1 recruitment. We finally show that R-loops and PRC1 can repress Polycomb-target genes in the absence of PRC2. Our results uncover an unanticipated synergy between R-loops and PRC1 in Polycomb repression mechanisms.
2019-03-19 | GSE118115 | GEO
Project description:1. Loss of RING1B substantially disrupts nuclear architecture. 2. PRC1 mediated looping can occur at a Mb scale and is independent of CTCF. 3. Polycomb mediated looping is driven by canonical PRC1 complexes. 4. Trimeric PRC1-mediated interactions occur in vitro and in vivo. 5. Gene up-regulation does not directly lead to the loss of PRC1 loops.
2019-12-15 | GSE134826 | GEO
Project description:Cell fate conversion is associated with extensive post translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and epigenetic factors. Akt1 kinase and PP2A phosphatase are key writer and eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3 embedded factors, such as Hdac4, Mef2c and Foxo1, form Hdac4 organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.
2024-02-19 | GSE255806 | GEO
Project description:We used whole-genome microarrays to identify the global transcriptional changes during biofilm dispersal and also to investigate the molecular mechanism that regulating biofilm dispersal.
2017-02-27 | GSE95377 | GEO
Project description:The rate, timing, and mode of species dispersal is recognized as a key driver of the structure and function of communities of macroorganisms, and may be one ecological process that determines the diversity of microbiomes. Many previous studies have quantified the modes and mechanisms of bacterial motility using monocultures of a few model bacterial species. But most microbes live in multispecies microbial communities, where direct interactions between microbes may inhibit or facilitate dispersal through a number of physical (e.g., hydrodynamic) and biological (e.g., chemotaxis) mechanisms, which remain largely unexplored. Using cheese rinds as a model microbiome, we demonstrate that physical networks created by filamentous fungi can impact the extent of small-scale bacterial dispersal and can shape the composition of microbiomes. From the cheese rind of Saint Nectaire, we serendipitously observed the bacterium Serratia proteamaculans actively spreads on networks formed by the fungus Mucor. By experimentally recreating these pairwise interactions in the lab, we show that Serratia spreads on actively growing and previously established fungal networks. The extent of symbiotic dispersal is dependent on the fungal network: diffuse and fast-growing Mucor networks provide the greatest dispersal facilitation of the Serratia species, while dense and slow-growing Penicillium networks provide limited dispersal facilitation. Fungal-mediated dispersal occurs in closely related Serratia species isolated from other environments, suggesting that this bacterial-fungal interaction is widespread in nature. Both RNA-seq and transposon mutagenesis point to specific molecular mechanisms that play key roles in this bacterial-fungal interaction, including chitin utilization and flagellin biosynthesis. By manipulating the presence and type of fungal networks in multispecies communities, we provide the first evidence that fungal networks shape the composition of bacterial communities, with Mucor networks shifting experimental bacterial communities to complete dominance by motile Proteobacteria. Collectively, our work demonstrates that these strong biophysical interactions between bacterial and fungi can have community-level consequences and may be operating in many other microbiomes.
2017-08-02 | GSE85095 | GEO
Project description:R-loops and PRC1 repress Polycomb-target genes in mouse embryonic stem cells
| PRJNA484502 | ENA
Project description:14-3-3 binding motif phosphorylation disrupts Hdac4 organized condensates to stimulate cardiac reprogramming
| PRJNA1076560 | ENA
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:Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. In addition, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we discovered that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not associated with loss of repressive Polycomb chromatin modifications. Instead, loss of PDS5A leads to aberrant cohesin activity, ectopic insulation sites and specific reduction of ultra-long Polycomb loops. We infer that these loops are important for robust silencing at a subset of Polycomb target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.
2023-11-10 | GSE194268 | GEO