Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces, revealed the extent and complexity of the AdpA regulatory network.
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ABSTRACT:
ORGANISM(S): Streptomyces griseus
PROVIDER: GSE33994 | GEO | 2012/04/04
SECONDARY ACCESSION(S): PRJNA150637
REPOSITORIES: GEO
Similar Datasets
Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences the expression of >1000 genes; however, the overall picture of the AdpA regulon remains obscure. Here, we took snapshots of the distribution of AdpA across the chromosome in living S. griseus cells using chromatin immunoprecipitation/chromatin affinity precipitation-seq analysis. In both liquid and solid cultures, AdpA bound to >1200 similar sites, which were located on not only in putative regulatory regions (65%), but also in regions (35%) that appeared not to affect transcription. Transcriptome analysis indicated that ~40% of the AdpA-binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures, despite their similar AdpA-binding profiles. We concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins. A comprehensive competitive gel mobility shift assay of AdpA with 304 selected AdpA-binding sites revealed several unique characteristics of the DNA-binding property of AdpA. This study provides the first experimental insight into the extent of the AdpA regulon, indicating that many genes are under the direct control of AdpA.
| S-EPMC3372375 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE33992: Streptomyces griseus transcriptome analysis in solid culture with delta adpA, encoding a global transcriptional regulator involved in morphological differentiation and secondary metabolism GSE33993: Streptomyces griseus transcriptome analysis in liquid culture with delta adpA, encoding a global transcriptional regulator involved in morphological differentiation and secondary metabolism GSE34036: Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces [liquid] GSE34037: Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces [solid] Refer to individual Series
2012-04-03 | E-GEOD-33994 | biostudies-arrayexpress
Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA.
2012-04-04 | GSE34037 | GEO
Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA.
2012-04-04 | GSE34036 | GEO
Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA. Analysis of genome-wide distribution of AdpA on liquid culture with two different methods to isolate AdpA-DNA complex
2012-04-03 | E-GEOD-34036 | biostudies-arrayexpress
Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA. Time course analysis of genome-wide distribution of AdpA on solid culture
2012-04-03 | E-GEOD-34037 | biostudies-arrayexpress
Project description:Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces, revealed the extent and complexity of the AdpA regulatory network.
| PRJNA150637 | ENA
Project description:The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multilevel regulations at transcriptional, posttranscriptional, and translational levels, yet no posttranslational regulation has been reported. Sulfane sulfur, such as hydro polysulfide (HSnH, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), is common inside microorganisms, but its physiological functions are largely unclear. Here, we discovered that sulfane sulfur posttranslationally modifies AdpA in Streptomyces coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis, and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCE Streptomyces species produce a myriad of natural products with (potential) clinical applications. While the database of biosynthetic gene clusters is quickly expanding, their regulation mechanisms are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Here, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is that sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation-related genes, to form sulfhydrated AdpA. This modification changes the dynamics of AdpA-controlled gene networks and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of all AdpA-controlled biosynthetic pathways. Thus, this finding provides a new strategy for mining and activating valuable biosynthetic gene clusters.
| S-EPMC9239190 | biostudies-literature
Project description:In members of genus Streptomyces, AdpA is a master transcriptional regulator that controls the expression of hundreds of genes involved in morphological differentiation, secondary metabolite biosynthesis, chromosome replication, etc. However, the function of AdpASv, an AdpA ortholog of Streptomyces venezuelae, is unknown. This bacterial species is a natural producer of chloramphenicol and has recently become a model organism for studies on Streptomyces. Here, we demonstrate that AdpASv is essential for differentiation and antibiotic biosynthesis in S. venezuelae and provide evidence suggesting that AdpASv positively regulates its own gene expression. We speculate that the different modes of AdpA-dependent transcriptional autoregulation observed in S. venezuelae and other Streptomyces species reflect the arrangement of AdpA binding sites in relation to the transcription start site. Lastly, we present preliminary data suggesting that AdpA may undergo a proteolytic processing and we speculate that this may potentially constitute a novel regulatory mechanism controlling cellular abundance of AdpA in Streptomyces. IMPORTANCEStreptomyces are well-known producers of valuable secondary metabolites which include a large variety of antibiotics and important model organisms for developmental studies in multicellular bacteria. The conserved transcriptional regulator AdpA of Streptomyces exerts a pleiotropic effect on cellular processes, including the morphological differentiation and biosynthesis of secondary metabolites. Despite extensive studies, the function of AdpA in these processes remains elusive. This work provides insights into the role of a yet unstudied AdpA ortholog of Streptomyces venezuelae, now considered a novel model organism. We found that AdpA plays essential role in morphological differentiation and biosynthesis of chloramphenicol, a broad-spectrum antibiotic. We also propose that AdpA may undergo a proteolytic processing that presumably constitutes a novel mechanism regulating cellular abundance of this master regulator.
| S-EPMC8653842 | biostudies-literature
Project description:To identify genes regulated by AdpA in liquid culture, transcriptome profiles between delta adpA strains with his-adpA and control delta adpA strains were analyzed.
2012-04-04 | GSE33993 | GEO