scholarly journals Interplay between nucleoid-associated proteins and transcription factors in controlling specialized metabolism in Streptomyces

2021 ◽  
Author(s):  
Xiafei Zhang ◽  
Sara N. Andres ◽  
Marie A. Elliot
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Antibiotic Production ◽  
Biosynthetic Gene Cluster ◽  
Regulatory Proteins ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Associated Proteins ◽  
Insight Into

Lsr2 is a small nucleoid-associated protein found throughout the actinobacteria. Lsr2 functions similarly to the well-studied H-NS, in that it preferentially binds AT-rich sequences and represses gene expression. In Streptomyces venezuelae, Lsr2 represses the expression of many specialized metabolic clusters, including the chloramphenicol antibiotic biosynthetic gene cluster, and deleting lsr2 leads to significant upregulation of chloramphenicol cluster expression. We show here that Lsr2 likely exerts its repressive effects on the chloramphenicol cluster by polymerizing along the chromosome, and by bridging sites within and adjacent to the chloramphenicol cluster. CmlR is a known activator of the chloramphenicol cluster, but expression of its associated gene is not upregulated in an lsr2 mutant strain. We demonstrate that CmlR is essential for chloramphenicol production, and further reveal that CmlR functions to 'counter-silence' Lsr2's repressive effects by recruiting RNA polymerase and enhancing transcription, with RNA polymerase effectively clearing bound Lsr2 from the chloramphenicol cluster DNA. Our results provide insight into the interplay between opposing regulatory proteins that govern antibiotic production in S. venezuelae, which could be exploited to maximize the production of bioactive natural products in other systems.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

scholarly journals Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zi Wang ◽  
Pan Wang ◽  
Yanan Li ◽  
Hongling Peng ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Hematological Malignancies ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hematologic Disorders ◽  
Cell Lineages ◽  
Stage Of Development ◽  
Transcription Complexes ◽  
Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

Biosynthesis of the uridine-derived nucleoside antibiotic A-94964: identification and characterization of the biosynthetic gene cluster provide insight into the biosynthetic pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Biosynthetic Pathway ◽  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Identification And Characterization ◽  
Insight Into

The biosynthetic pathway of the uridine-derived nucleoside antibiotic A-94964 was proposed via in silico analysis coupled with gene deletion experiments.

scholarly journals Unraveling the regulation of sophorolipid biosynthesis in Starmerella bombicola

2020 ◽  
Vol 20 (3) ◽  
Author(s):  
Sofie Lodens ◽  
Sophie L K W Roelants ◽  
Goedele Luyten ◽  
Robin Geys ◽  
Pieter Coussement ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stationary Phase ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Exponential Phase ◽  
Biosynthetic Gene ◽  
Reporter System ◽  
Gfp Expression ◽  
Qpcr Analysis ◽  
Starmerella Bombicola

ABSTRACT Starmerella bombicola very efficiently produces the secondary metabolites sophorolipids (SLs). Their biosynthesis is not-growth associated and highly upregulated in the stationary phase. Despite high industrial and academic interest, the underlying regulation of SL biosynthesis remains unknown. In this paper, potential regulation of SL biosynthesis through the telomere positioning effect (TPE) was investigated, as the SL gene cluster is located adjacent to a telomere. An additional copy of this gene cluster was introduced elsewhere in the genome to investigate if this results in a decoy of regulation. Indeed, for the new strain, the onset of SL production was shifted to the exponential phase. This result was confirmed by RT-qPCR analysis. The TPE effect was further investigated by developing and applying a suitable reporter system for this non-conventional yeast, enabling non-biased comparison of gene expression between the subtelomeric CYP52M1- and the URA3 locus. This was done with a constitutive endogenous promotor (pGAPD) and one of the endogenous promotors of the SL biosynthetic gene cluster (pCYP52M1). A clear positioning effect was observed for both promotors with significantly higher GFP expression levels at the URA3 locus. No clear GFP upregulation was observed in the stationary phase for any of the new strains.

scholarly journals Core regulatory circuitries in defining cancer cell identity across the malignant spectrum

Open Biology ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 200121
Author(s):  
Leila Jahangiri ◽  
Loukia Tsaprouni ◽  
Ricky M. Trigg ◽  
John A. Williams ◽  
Georgios V. Gkoutos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Chromatin Structure ◽  
Drug Targets ◽  
Genetic Alterations ◽  
Specific Gene ◽  
Molecular Dissection ◽  
Cell Identity ◽  
Lineage Specific Gene

Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models.

scholarly journals Unraveling a Tangled Skein: Evolutionary Analysis of the Bacterial Gibberellin Biosynthetic Operon

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Ryan S. Nett ◽  
Huy Nguyen ◽  
Raimund Nagel ◽  
Ariana Marcassa ◽  
Trevor C. Charles ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Genetic Heterogeneity ◽  
Evolutionary History ◽  
Biosynthetic Gene Cluster ◽  
Evolutionary Analysis ◽  
Biosynthetic Gene ◽  
Ancestral Gene ◽  
Associated Bacteria ◽  
Microbe Interactions ◽  
Insight Into

ABSTRACT Gibberellin (GA) phytohormones are ubiquitous regulators of growth and developmental processes in vascular plants. The convergent evolution of GA production by plant-associated bacteria, including both symbiotic nitrogen-fixing rhizobia and phytopathogens, suggests that manipulation of GA signaling is a powerful mechanism for microbes to gain an advantage in these interactions. Although orthologous operons encode GA biosynthetic enzymes in both rhizobia and phytopathogens, notable genetic heterogeneity and scattered operon distribution in these lineages, including loss of the gene for the final biosynthetic step in most rhizobia, suggest varied functions for GA in these distinct plant-microbe interactions. Therefore, deciphering GA operon evolutionary history should provide crucial evidence toward understanding the distinct biological roles for bacterial GA production. To further establish the genetic composition of the GA operon, two operon-associated genes that exhibit limited distribution among rhizobia were biochemically characterized, verifying their roles in GA biosynthesis. This enabled employment of a maximum parsimony ancestral gene block reconstruction algorithm to characterize loss, gain, and horizontal gene transfer (HGT) of GA operon genes within alphaproteobacterial rhizobia, which exhibit the most heterogeneity among the bacteria containing this biosynthetic gene cluster. Collectively, this evolutionary analysis reveals a complex history for HGT of the entire GA operon, as well as the individual genes therein, and ultimately provides a basis for linking genetic content to bacterial GA functions in diverse plant-microbe interactions, including insight into the subtleties of the coevolving molecular interactions between rhizobia and their leguminous host plants. IMPORTANCE While production of phytohormones by plant-associated microbes has long been appreciated, identification of the gibberellin (GA) biosynthetic operon in plant-associated bacteria has revealed surprising genetic heterogeneity. Notably, this heterogeneity seems to be associated with the lifestyle of the microbe; while the GA operon in phytopathogenic bacteria does not seem to vary to any significant degree, thus enabling production of bioactive GA, symbiotic rhizobia exhibit a number of GA operon gene loss and gain events. This suggests that a unique set of selective pressures are exerted on this biosynthetic gene cluster in rhizobia. Through analysis of the evolutionary history of the GA operon in alphaproteobacterial rhizobia, which display substantial diversity in their GA operon structure and gene content, we provide insight into the effect of lifestyle and host interactions on the production of this phytohormone by plant-associated bacteria.

scholarly journals Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

Toxins ◽  
2013 ◽  
Vol 5 (8) ◽  
pp. 1422-1446 ◽  
Author(s):  
Barry Scott ◽  
Carolyn Young ◽  
Sanjay Saikia ◽  
Lisa McMillan ◽  
Brendon Monahan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Gene Expression Analyses ◽  
Penicillium Paxilli

scholarly journals DksA-dependent regulation of RpoS contributes to Borrelia burgdorferi tick-borne transmission and mammalian infectivity

2021 ◽  
Vol 17 (2) ◽  
pp. e1009072
Author(s):  
William K. Boyle ◽  
Crystal L. Richards ◽  
Daniel P. Dulebohn ◽  
Amanda K. Zalud ◽  
Jeff A. Shaw ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Nutrient Limitation ◽  
Pathogenic Bacteria ◽  
Transcriptional Control ◽  
Ixodes Scapularis ◽  
Stringent Response ◽  
Transcriptional Responses

Throughout its enzootic cycle, the Lyme disease spirochete Borreliella (Borrelia) burgdorferi, senses and responds to changes in its environment using a small repertoire of transcription factors that coordinate the expression of genes required for infection of Ixodes ticks and various mammalian hosts. Among these transcription factors, the DnaK suppressor protein (DksA) plays a pivotal role in regulating gene expression in B. burgdorferi during periods of nutrient limitation and is required for mammalian infectivity. In many pathogenic bacteria, the gene regulatory activity of DksA, along with the alarmone guanosine penta- and tetra-phosphate ((p)ppGpp), coordinate the stringent response to various environmental stresses, including nutrient limitation. In this study, we sought to characterize the role of DksA in regulating the transcriptional activity of RNA polymerase and its role in the regulation of RpoS-dependent gene expression required for B. burgdorferi infectivity. Using in vitro transcription assays, we observed recombinant DksA inhibits RpoD-dependent transcription by B. burgdorferi RNA polymerase independent of ppGpp. Additionally, we determined the pH-inducible expression of RpoS-dependent genes relies on DksA, but this relationship is independent of (p)ppGpp produced by Relbbu. Subsequent transcriptomic and western blot assays indicate DksA regulates the expression of BBD18, a protein previously implicated in the post-transcriptional regulation of RpoS. Moreover, we observed DksA was required for infection of mice following intraperitoneal inoculation or for transmission of B. burgdorferi by Ixodes scapularis nymphs. Together, these data suggest DksA plays a central role in coordinating transcriptional responses in B. burgdorferi required for infectivity through DksA’s interactions with RNA polymerase and post-transcriptional control of RpoS.

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