Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-layered inhibition of Streptomyces development: BldO is a dedicated repressor of whiB.

ABSTRACT: BldD-(c-di-GMP) sits on top of the regulatory network that controls differentiation in Streptomyces, repressing a large regulon of developmental genes when the bacteria are growing vegetatively. In this way, BldD functions as an inhibitor that blocks the initiation of sporulation. Here, we report the identification and characterisation of BldO, an additional developmental repressor that acts to sustain vegetative growth and prevent entry into sporulation. However, unlike the pleiotropic regulator BldD, we show that BldO functions as the dedicated repressor of a single key target gene, whiB, and that deletion of bldO or constitutive expression of whiB is sufficient to induce precocious hypersporulation.

SUBMITTER: Bush MJ

PROVIDER: S-EPMC5485038 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Multi-layered inhibition of Streptomyces development: BldO is a dedicated repressor of whiB.

Bush Matthew J MJ Chandra Govind G Findlay Kim C KC Buttner Mark J MJ

Molecular microbiology 20170327 5

BldD-(c-di-GMP) sits on top of the regulatory network that controls differentiation in Streptomyces, repressing a large regulon of developmental genes when the bacteria are growing vegetatively. In this way, BldD functions as an inhibitor that blocks the initiation of sporulation. Here, we report the identification and characterisation of BldO, an additional developmental repressor that acts to sustain vegetative growth and prevent entry into sporulation. However, unlike the pleiotropic regulato ...[more]

PMID: 28271577

Similar Datasets

Mutually repressing repressor functions and multi-layered cellular heterogeneity regulate the bistable Salmonella fliC census.

Project description:Bistable flagellar and virulence gene expression generates specialized Salmonella subpopulations with distinct functions. Repressing flagellar genes allows Salmonella to evade caspase-1 mediated host defenses and enhances systemic colonization. By definition, bistability arises when intermediate states of gene expression are rendered unstable by the underlying genetic circuitry. We demonstrate sustained bistable fliC expression in virulent Salmonella 14028 and document dynamic control of the distribution, or single-cell census, of flagellar gene expression by the mutually repressing repressors YdiV and FliZ. YdiV partitions cells into the fliC-OFF subpopulation, while FliZ partitions cells into the fliC-HIGH subpopulation at late time points during growth. Bistability of ΔfliZ populations and ydiV-independent FliZ control of flagellar gene expression provide evidence that the YdiV-FliZ mutually repressing repressor circuit is not required for bistability. Repression and activation by YdiV and FliZ (respectively) can shape the census of fliC expression independently, and bistability collapses into a predominantly intermediate population in the absence of both regulators. Metered expression of YdiV and FliZ reveals variable sensitivity to these regulators and defines conditions where expression of FliZ enhances fliC expression and where FliZ does not alter the fliC census. Thus, this evolved genetic circuitry coordinates multiple layers of regulatory heterogeneity into a binary response.

| S-EPMC4262692 | biostudies-literature

WhiD and WhiB, homologous proteins required for different stages of sporulation in Streptomyces coelicolor A3(2).

Project description:The whiD locus, which is required for the differentiation of Streptomyces coelicolor aerial hyphae into mature spore chains, was localized by map-based cloning to the overlap between cosmids 6G4 and D63 of the minimal ordered library of Redenbach et al. (M. Redenbach et al., Mol. Microbiol. 21:77-96, 1996). Subcloning and sequencing showed that whiD encodes a homologue of WhiB, a protein required for the initiation of sporulation septation in S. coelicolor. WhiD and WhiB belong to a growing family of small (76- to 112-residue) proteins of unknown biochemical function in which four cysteines are absolutely conserved; all known members of this family are found in the actinomycetes. A constructed whiD null mutant showed reduced levels of sporulation, and those spores that did form were heat sensitive, lysed extensively, and were highly irregular in size, arising at least in part from irregularity in septum placement. The whiD null mutant showed extreme variation in spore cell wall deposition; most spores had uniformly thin (20- to 30-nm) walls, but spore chains were frequently observed in which there was irregular but very pronounced (up to 170 nm) cell wall thickening at the junctions between spores. whiD null mutant spores were frequently partitioned into irregular smaller units through the deposition of additional septa, which were often laid down in several different planes, very close to the spore poles. These "minicompartments" appeared to be devoid of chromosomal DNA. Two whiD promoters, whiDp1 and whiDp2, were identified, and their activities were analyzed during development of wild-type S. coelicolor on solid medium. Both promoters were developmentally regulated; whiDp1 and whiDp2 transcripts were detected transiently, approximately at the time when sporulation septa were observed in the aerial hyphae.

| S-EPMC94414 | biostudies-literature

Development of multi-layered and multi-sensitive polymeric nanocontainers for cancer therapy: in vitro evaluation.

Project description:Nanoscale drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, hollow polymeric nanocontainers have attracted great interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of stimuli-responsive materials capable of responding to the biochemical alterations of the tumour microenvironment. Here are reported the synthesis, characterization and in vitro evaluation of a three-stimuli-sensitive hollow nanocontainer consisting of three different shells, each one sensitive to a specific tumoral stimulus: in order pH, temperature and reducing environment. To test its properties, daunorubicin was used as a model drug, for which the nanocontainers exhibited excellent encapsulation ability. The in vitro drug release behaviour was studied under different conditions, where the system proved capable of responding to the selected tumoral stimuli by releasing a larger amount of drug than in physiological environment. The hollow system itself showed negligible cytotoxicity but the loaded nanocontainers and free drug showed identical cytotoxicity and intracellular localization. Therefore, this formulation can be considered as a promising platform to develop an injectable delivery system capable of improving systematic toxicity without affecting or reducing the activity of the encapsulated drug.

| S-EPMC6168533 | biostudies-other

Variational autoencoding of gene landscapes during mouse CNS development uncovers layered roles of Polycomb Repressor Complex 2.

Project description:A prominent aspect of most, if not all, central nervous systems (CNSs) is that anterior regions (brain) are larger than posterior ones (spinal cord). Studies in Drosophila and mouse have revealed that Polycomb Repressor Complex 2 (PRC2), a protein complex responsible for applying key repressive histone modifications, acts by several mechanisms to promote anterior CNS expansion. However, it is unclear what the full spectrum of PRC2 action is during embryonic CNS development and how PRC2 intersects with the epigenetic landscape. We removed PRC2 function from the developing mouse CNS, by mutating the key gene Eed, and generated spatio-temporal transcriptomic data. To decode the role of PRC2, we developed a method that incorporates standard statistical analyses with probabilistic deep learning to integrate the transcriptomic response to PRC2 inactivation with epigenetic data. This multi-variate analysis corroborates the central involvement of PRC2 in anterior CNS expansion, and also identifies several unanticipated cohorts of genes, such as proliferation and immune response genes. Furthermore, the analysis reveals specific profiles of regulation via PRC2 upon these gene cohorts. These findings uncover a differential logic for the role of PRC2 upon functionally distinct gene cohorts that drive CNS anterior expansion. To support the analysis of emerging multi-modal datasets, we provide a novel bioinformatics package that integrates transcriptomic and epigenetic datasets to identify regulatory underpinnings of heterogeneous biological processes.

| S-EPMC8860581 | biostudies-literature

Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development.

Project description:Hematopoietic stem cells (HSCs) first emerge in the embryonic aorta-gonad-mesonephros (AGM) region. Studies of model organisms defined intersecting signaling pathways that converge to promote HSC emergence predominantly in the ventral domain of the dorsal aorta. Much less is known about mechanisms driving HSC development in humans. Here, to identify secreted signals underlying human HSC development, we combined spatial transcriptomics analysis of dorsoventral polarized signaling in the aorta with gene expression profiling of sorted cell populations and single cells. Our analysis revealed a subset of aortic endothelial cells with a downregulated arterial signature and a predicted lineage relationship with the emerging HSC/progenitor population. Analysis of the ventrally polarized molecular landscape identified endothelin 1 as an important secreted regulator of human HSC development. The obtained gene expression datasets will inform future studies on mechanisms of HSC development in vivo and on generation of clinically relevant HSCs in vitro.

| S-EPMC7671940 | biostudies-literature

Multi-layered population structure in Island Southeast Asians

Project description:The history of human settlement in Southeast Asia has been complex and involved several distinct dispersal events. Here we report the analyses of 1825 individuals from Southeast Asia including new genome-wide genotype data for 146 individuals from three Mainland Southeast Asian (Burmese, Malay and Vietnamese) and four Island Southeast Asian (Dusun, Filipino, Kankanaey and Murut) populations. While confirming the presence of previously recognized major ancestry components in the Southeast Asian population structure, we highlight the Kankanaey Igorots from the highlands of the Philippine Mountain Province as likely the closest living representatives of the source population that may have given rise to the Austronesian expansion. This conclusion rests on independent evidence from various analyses of autosomal data and uniparental markers.

2016-02-04 | GSE77508 | GEO

Mapping multi-layered regulation in response to environmental stress

Project description:We have mapped transcript and protein concentrations in cervical cancer cells responding to treatment with tunicamycin over an eight hour time course. We complement this dataset with RNA footprints of ribosomes and non-ribosomal proteins to determine changes in translation and trans-factor binding. The goals of this study are to unveil the time dependent complexity of the signaling pathways at the level of transcription and translation during different stress conditions like stress of the endoplasmic reticulum and oxidative stress.

2018-10-08 | GSE113171 | GEO

Development of a multi-layered psychosocial care system for children in areas of political violence.

Project description:Few psychosocial and mental health care systems have been reported for children affected by political violence in low- and middle income settings and there is a paucity of research-supported recommendations. This paper describes a field tested multi-layered psychosocial care system for children (focus age between 8-14 years), aiming to translate common principles and guidelines into a comprehensive support package. This community-based approach includes different overlapping levels of interventions to address varying needs for support. These levels provide assessment and management of problems that range from the social-pedagogic domain to the psychosocial, the psychological and the psychiatric domains. Specific intervention methodologies and their rationale are described within the context of a four-country program (Burundi, Sri Lanka, Indonesia and Sudan). The paper aims to contribute to bridge the divide in the literature between guidelines, consensus & research and clinical practice in the field of psychosocial and mental health care in low- and middle-income countries.

| S-EPMC2907307 | biostudies-literature

Emerging RUNX2-Mediated Gene Regulatory Mechanisms Consisting of Multi-Layered Regulatory Networks in Skeletal Development.

Project description:Skeletal development is tightly coordinated by chondrocytes and osteoblasts, which are derived from skeletal progenitors, and distinct cell-type gene regulatory programs underlie the specification and differentiation of cells. Runt-related transcription factor 2 (Runx2) is essential to chondrocyte hypertrophy and osteoblast differentiation. Genetic studies have revealed the biological functions of Runx2 and its involvement in skeletal genetic diseases. Meanwhile, molecular biology has provided a framework for our understanding of RUNX2-mediated transactivation at a limited number of cis-regulatory elements. Furthermore, studies using next-generation sequencing (NGS) have provided information on RUNX2-mediated gene regulation at the genome level and novel insights into the multiple layers of gene regulatory mechanisms, including the modes of action of RUNX2, chromatin accessibility, the concept of pioneer factors and phase separation, and three-dimensional chromatin organization. In this review, I summarize the emerging RUNX2-mediated regulatory mechanism from a multi-layer perspective and discuss future perspectives for applications in the treatment of skeletal diseases.

| S-EPMC9917854 | biostudies-literature

Integrative spatial analysis reveals a multi-layered organization of glioblastoma

Project description:Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics with novel computational approaches to uncover the organization of glioma cellular states. We find three prominent modes of organization. First, cells in any given state tend to be spatially clustered, with local environments that are each enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. Third, the pairwise interactions that we detect collectively define a global architecture composed of five layers. Hypoxia appears to drive this 5-layered organization, as it is associated with a long-range organization that extends from the hypoxic core to the infiltrative edge of the tumor. Accordingly, tumor regions distant from any hypoxic foci are less organized. In summary, we provide a conceptual framework for the organization of gliomas and highlight the role of hypoxia as a potential long-range tissue organizer.

2024-02-18 | GSE237183 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data