Role of Epigenetics in Unicellular to Multicellular Transition in Dictyostelium
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ABSTRACT:
PROVIDER: PRJNA565988 | ENA |
REPOSITORIES: ENA
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Project description:The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that exists in both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity. While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and syntenic analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity. These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate the evolution of multicellularity.
2021-06-15 | PXD024225 | panorama
Project description: Not available
| S-EPMC8094536 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-04-21 | GSE137604 | GEO
Project description:In many developmental systems, morphogenesis is coupled with dramatic changes in spatiotemporal gene expression, often orchestrated by the coordinated action of transcription factors. Development of the social soil amoebae Dictyostelium discoideum proceeds through a sequence of morphological and transcriptional changes, but the role of transcription factors in development is not well understood. GtaC, a GATA-type zinc-finger transcription factor, is essential for Dictyostelium development. It decodes pulsatile extracellular cAMP signals during early development and mediates cell-type differentiation at later stages. Here, we studied the developmental regulatory roles of GtaC through the concerted analysis of temporal ChIP- and RNA-sequencing data from strains that carry different alleles of gtaC. We show that GtaC exhibits temporally distinctive DNA-binding patterns throughout early development, accompanied by largely cotemporaneous expression of its target genes. We also show that GtaC binds DNA in two modes. One of these modes exhibits binding preferences for canonical GATA-like sequences, the regulatory consequences accompanying which is predominantly up-regulation of target gene expression. The other binding mode is mostly associated with down-regulation. Among its targets we find transcription factors that are essential for development as well as genes involved in cAMP signaling and cell-type specification. Our results suggest that GtaC is a master regulator that regulates multiple physiological processes during early development, when Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism. Cotemporaneous transcriptional profiling and ChIP sequencing during early Dictyostelium development
2015-07-02 | E-GEOD-63151 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7915506 | biostudies-literature
Project description:Dictyostelium discoideum behavior depends on nutrients. When sufficient food is present these amoebae exist in a unicellular state (vegetative growth), but upon starvation they aggregate into a multicellular organism (developmental growth). For proteomics 30 minutes and eight hour cultures of D. discoideum under vegetative and starved growth conditions were compared by DIA-LFQ. This unique biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. We show here that reactive oxygen species (ROS), generated as a consequence of nutrient limitation, lead to the sequestration of the amino acid cysteine in the antioxidant glutathione, limiting the use of its sulfur atom for processes such as protein translation and FeS cluster-containing enzyme activity that contribute to mitochondrial metabolism and cellular proliferation. Such regulated sulfur sequestration maintains D. discoideum in a non-proliferating state that paves the way for multicellular development. This new mechanism of ROS signaling highlights oxygen and sulfur as simple, early evolutionary signaling molecules dictating cell fate, with implications for responses to nutrient fluctuations in higher eukaryotes.
2021-03-23 | PXD023404 | Pride
Project description:In many developmental systems, morphogenesis is coupled with dramatic changes in spatiotemporal gene expression, often orchestrated by the coordinated action of transcription factors. Development of the social soil amoebae Dictyostelium discoideum proceeds through a sequence of morphological and transcriptional changes, but the role of transcription factors in development is not well understood. GtaC, a GATA-type zinc-finger transcription factor, is essential for Dictyostelium development. It decodes pulsatile extracellular cAMP signals during early development and mediates cell-type differentiation at later stages. Here, we studied the developmental regulatory roles of GtaC through the concerted analysis of temporal ChIP- and RNA-sequencing data from strains that carry different alleles of gtaC. We show that GtaC exhibits temporally distinctive DNA-binding patterns throughout early development, accompanied by largely cotemporaneous expression of its target genes. We also show that GtaC binds DNA in two modes. One of these modes exhibits binding preferences for canonical GATA-like sequences, the regulatory consequences accompanying which is predominantly up-regulation of target gene expression. The other binding mode is mostly associated with down-regulation. Among its targets we find transcription factors that are essential for development as well as genes involved in cAMP signaling and cell-type specification. Our results suggest that GtaC is a master regulator that regulates multiple physiological processes during early development, when Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism.
2015-07-02 | GSE63151 | GEO
Project description:The extent to which mRNA and protein levels correlate is still not fully known, especially during development, when cells undergo a major transition in gene expression. One organism with particular development is Dictyostelium discoideum, during which it transitions from free-living unicellular to multicellular. Previously the transcriptome has been thoroughly studied during multicellular development, however the proteome and its correlation to the transcriptome during this transition is not fully understood.
In this study, for the first time, paired transcriptomics and proteomics was performed in a time series during aggregative multicellularity. From the analysis, the majority of transcripts were identified as differentially expressed, and we could quantify roughly a third of the proteome during early multicellular development. The proteome and transcriptome correlate relatively highly during steady-state, however this decreases as soon as multicellular aggregation is initiated. Correlation is particularly low at the gene-level during development. We find that dynamically regulated mRNA often leads to linear up- or downregulation of the protein, and that there is a time lag of approximately 2 to 4 hours between mRNA and protein.
2023-12-09 | MSV000093620 | MassIVE
Project description:Like most eukaryotes, the pre-metazoan social amoeba Dictyostelium depends on the SCF (Skp1/cullin-1/F-box protein) family of E3 ubiquitin ligases to regulate its proteome. In Dictyostelium, starvation induces a transition from unicellular feeding to a multicellular slug that responds to external signals to culminate into a fruiting body containing terminally differentiated stalk and spore cells. These transitions are subject to regulation by F-box proteins and O2-dependent posttranslational modifications of Skp1. Here we examine in greater depth the essential role of FbxW2 and Vwa1, which was found in the FbxWD interactome by co-immunoprecipitation and is classified as a vault protein inter-alpha- trypsin (VIT) and von Willebrand factor-A (vWFA) domain containing protein. Reciprocal co-IPs using gene-tagged strains confirmed the interaction and their similar transcript expression profiles during multicellular development suggest they function together. FbxWD overexpression and proteasome inhibitors did not affect Vwa1 levels suggesting a non-substrate relationship. Forced FbxwD overexpression in slug tip cells where it is normally expressed blocked culmination by a mechanism that depended on its F-box and RING domains, and on Vwa1 expression itself. However, vwa1-disruption alone did not affect development. In contrast, overexpression of either of its three conserved domains arrested development but the effect depended on Vwa1 expression. Based on structure predictions, we propose that the Vwa1 domains exert their negative effect by artificially activating Vwa1 which in turn imbalances its synergistic function with FbxWD. Autoinhibition or homodimerization might be relevant to the poorly understood tumor suppressor role of the evolutionarily related VWA5A/BCSC-1 in humans.
2023-10-24 | PXD035634 | Pride
Project description:Like most eukaryotes, the pre-metazoan social amoeba Dictyostelium depends on the SCF (Skp1/cullin-1/F-box protein) family of E3 ubiquitin ligases to regulate its proteome. In Dictyostelium, starvation induces a transition from unicellular feeding to a multicellular slug that responds to external signals to culminate into a fruiting body containing terminally differentiated stalk and spore cells. These transitions are subject to regulation by F-box proteins and O2-dependent posttranslational modifications of Skp1. Here we examine in greater depth the essential role of FbxW2 and Vwa1, which was found in the FbxWD interactome by co-immunoprecipitation and is classified as a vault protein inter-alpha- trypsin (VIT) and von Willebrand factor-A (vWFA) domain containing protein. Reciprocal co-IPs using gene-tagged strains confirmed the interaction and their similar transcript expression profiles during multicellular development suggest they function together. FbxWD overexpression and proteasome inhibitors did not affect Vwa1 levels suggesting a non-substrate relationship. Forced FbxwD overexpression in slug tip cells where it is normally expressed blocked culmination by a mechanism that depended on its F-box and RING domains, and on Vwa1 expression itself. However, vwa1-disruption alone did not affect development. In contrast, overexpression of either of its three conserved domains arrested development but the effect depended on Vwa1 expression. Based on structure predictions, we propose that the Vwa1 domains exert their negative effect by artificially activating Vwa1 which in turn imbalances its synergistic function with FbxWD. Autoinhibition or homodimerization might be relevant to the poorly understood tumor suppressor role of the evolutionarily related VWA5A/BCSC-1 in humans.
2023-10-24 | PXD035633 | Pride