scholarly journals The bZIP Transcription Factor MeaB Mediates Nitrogen Metabolite Repression at Specific Loci

2010 ◽  
Vol 9 (10) ◽  
pp. 1588-1601 ◽  
Author(s):  
Dominik Wagner ◽  
Anne Schmeinck ◽  
Magdalena Mos ◽  
Igor Y. Morozov ◽  
Mark X. Caddick ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Double Mutant ◽  
Nitrogen Limitation ◽  
Sufficient Conditions ◽  
Bzip Transcription Factor ◽  
Fusarium Fujikuroi ◽  
Dependent Manner ◽  
Content Type ◽  
Nitrogen Metabolite Repression

ABSTRACT In Fusarium fujikuroi, bikaverin (BIK) biosynthesis is subject to repression by nitrogen. Unlike most genes subject to nitrogen metabolite repression, it has been shown that transcription of bik biosynthetic genes is not AreA dependent. Searching for additional transcription factors that may be involved in nitrogen regulation, we cloned and characterized the orthologue of Aspergillus nidulans meaB, which encodes a bZIP transcription factor. Two transcripts are derived from F. fujikuroi meaB: the large transcript (meaB L) predominates under nitrogen-sufficient conditions and the smaller transcript (meaB S) under nitrogen limitation, in an AreA-dependent manner. MeaB is specifically translocated to the nucleus under nitrogen-sufficient conditions in both F. fujikuroi and A. nidulans. Deletion of meaB resulted in partial upregulation of several nitrogen-regulated genes, but only in the ΔmeaB ΔareA double mutant were the bikaverin genes significantly upregulated in the presence of glutamine. These data demonstrate that MeaB and AreA coordinately mediate nitrogen metabolite repression and, importantly, that independently of AreA, MeaB can mediate nitrogen metabolite repression at specific loci in F. fujikuroi.

scholarly journals Transcription Factor ADS-4 Regulates Adaptive Responses and Resistance to Antifungal Azole Stress

2015 ◽  
Vol 59 (9) ◽  
pp. 5396-5404 ◽  
Author(s):  
Kangji Wang ◽  
Zhenying Zhang ◽  
Xi Chen ◽  
Xianyun Sun ◽  
Cheng Jin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Efflux Pump ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Bzip Transcription Factor ◽  
Azole Resistance ◽  
Homologous Gene ◽  
Adaptive Responses ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTAzoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. This study identified a bZIP transcription factor, ADS-4 (antifungaldrugsensitive-4), as a new regulator of adaptive responses and resistance to antifungal azoles. Transcription ofads-4inNeurospora crassacells increased when they were subjected to ketoconazole treatment, whereas the deletion ofads-4resulted in hypersensitivity to ketoconazole and fluconazole. In contrast, the overexpression ofads-4increased resistance to fluconazole and ketoconazole inN. crassa. Transcriptome sequencing (RNA-seq) analysis, followed by quantitative reverse transcription (qRT)-PCR confirmation, showed that ADS-4 positively regulated the transcriptional responses of at least six genes to ketoconazole stress inN. crassa. The gene products of four ADS-4-regulated genes are known contributors to azole resistance, including the major efflux pump CDR4 (Pdr5p ortholog), an ABC multidrug transporter (NcAbcB), sterol C-22 desaturase (ERG5), and a lipid transporter (NcRTA2) that is involved in calcineurin-mediated azole resistance. Deletion of theads-4-homologous gene Afads-4inAspergillus fumigatuscaused hypersensitivity to itraconazole and ketoconazole, which suggested that ADS-4 is a functionally conserved regulator of adaptive responses to azoles. This study provides important information on a new azole resistance factor that could be targeted by a new range of antifungal pesticides and drugs.

scholarly journals The Transcription Factor VdHapX Controls Iron Homeostasis and Is Crucial for Virulence in the Vascular Pathogen Verticillium dahliae

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Yonglin Wang ◽  
Chenglin Deng ◽  
Longyan Tian ◽  
Dianguang Xiong ◽  
Chengming Tian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Verticillium Dahliae ◽  
Iron Homeostasis ◽  
Pathogenic Fungi ◽  
Bzip Transcription Factor ◽  
Tree Seedlings ◽  
Iron Starvation ◽  
Content Type ◽  
Expression Of Genes ◽  
Increased Sensitivity

ABSTRACT Iron homeostasis is essential for full virulence and viability in many pathogenic fungi. Here, we showed that the bZip transcription factor VdHapX functions as a key regulator of iron homeostasis for adaptation to iron-depleted and iron-excess conditions and is required for full virulence in the vascular wilt fungus, Verticillium dahliae. Deletion of VdHapX impaired mycelial growth and conidiation under both iron starvation and iron sufficiency. Furthermore, disruption of VdHapX led to decreased formation of the long-lived survival structures of V. dahliae, known as microsclerotia. Expression of genes involved in iron utilization pathways and siderophore biosynthesis was misregulated in the ΔVdHapX strain under the iron-depleted condition. Additionally, the ΔVdHapX strain exhibited increased sensitivity to high iron concentrations and H2O2, indicating that VdHapX also contributes to iron or H2O2 detoxification. The ΔVdHapX strain showed a strong reduction in virulence on smoke tree seedlings (Cotinus coggygria) and was delayed in its ability to penetrate plant epidermal tissue. IMPORTANCE This study demonstrated that VdHapX is a conserved protein that mediates adaptation to iron starvation and excesses, affects microsclerotium formation, and is crucial for virulence of V. dahliae.

scholarly journals Expression of Adhesive Pili and the Collagen-Binding Adhesin Ace Is Activated by ArgR Family Transcription Factors inEnterococcus faecalis

2018 ◽  
Vol 200 (18) ◽  
Author(s):  
Dawn A. Manias ◽  
Gary M. Dunny
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Enterococcus Faecalis ◽  
Opportunistic Infections ◽  
Structural Genes ◽  
Gene Encoding ◽  
Collagen Binding ◽  
Content Type ◽  
Surface Adhesins

ABSTRACTIt was shown previously that the disruption of theahrCgene encoding a predicted ArgR family transcription factor results in a severe defect in biofilm formationin vitro, as well as a significant attenuation of virulence ofEnterococcus faecalisstrain OG1RF in multiple experimental infection models. Using transcriptome sequencing (RNA-seq), we observedahrC-dependent changes in the expression of more than 20 genes. AhrC-repressed genes included predicted determinants of arginine catabolism and several other metabolic genes and predicted transporters, while AhrC-activated genes included determinants involved in the production of surface protein adhesins. Most notably, the structural and regulatory genes of theebplocus encoding adhesive pili were positively regulated, as well as theacegene, encoding a collagen-binding adhesin. UsinglacZtranscription reporter fusions, we determined thatahrCand a secondargRtranscription factor gene,argR2, both function to activate the expression ofebpR, which directly activates the transcription of the pilus structural genes. Our data suggest that in the wild-typeE. faecalis, the low levels of EbpR limit the expression of pili and that biofilm biomass is also limited by the amount of pili expressed by the bacteria. The expression ofaceis similarly enhanced by AhrC and ArgR2, butaceexpression is not dependent on EbpR. Our results demonstrate the existence of novel regulatory cascades controlled by a pair of ArgR family transcription factors that might function as a heteromeric protein complex.IMPORTANCECell surface adhesins play critical roles in the formation of biofilms, host colonization, and the pathogenesis of opportunistic infections byEnterococcus faecalis. Here, we present new results showing that the expression of two major enterococcal surface adhesins,ebppili, and the collagen-binding protein Ace is positively regulated at the transcription level by twoargRfamily transcription factors, AhrC and ArgR2. In the case of pili, the direct target of regulation is theebpRgene, previously shown to activate the transcription of the pilus structural genes, while the activation ofacetranscription appears to be directly impacted by the two ArgR proteins. These transcription factors may represent new targets for blocking enterococcal infections.

scholarly journals Modulation of Pseudomonas aeruginosa Quorum Sensing by Glutathione

2019 ◽  
Vol 201 (9) ◽  
Author(s):  
Hui Zhou ◽  
Meizhen Wang ◽  
Nicole E. Smalley ◽  
Maxim Kostylev ◽  
Amy L. Schaefer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Quorum Sensing ◽  
Cell Density ◽  
Redox State ◽  
Gene Activation ◽  
Cellular Redox ◽  
Content Type ◽  
Cellular Redox State

ABSTRACT Pseudomonas aeruginosa uses quorum sensing (QS) to regulate the production of a battery of secreted products. At least some of these products are shared among the population and serve as public goods. When P. aeruginosa is grown on casein as the sole carbon and energy source, the QS-induced extracellular protease elastase is required for growth. We isolated a P. aeruginosa variant, which showed increased production of QS-induced factors after repeated transfers in casein broth. This variant, P. aeruginosa QS*, had a mutation in the glutathione synthesis gene gshA. We describe several experiments that show a gshA coding variant and glutathione affect the QS response. The P. aeruginosa QS transcription factor LasR has a redox-sensitive cysteine (C79). We report that GshA variant cells with a LasR C79S substitution show a similar QS response to that of wild-type P. aeruginosa. Surprisingly, it is not LasR but the QS transcription factor RhlR that is more active in bacteria containing the variant gshA. Our results demonstrate that QS integrates information about cell density and the cellular redox state via glutathione levels. IMPORTANCE Pseudomonas aeruginosa and other bacteria coordinate group behaviors using a chemical communication system called quorum sensing (QS). The QS system of P. aeruginosa is complex, with several regulators and signals. We show that decreased levels of glutathione lead to increased gene activation in P. aeruginosa, which did not occur in a strain carrying the redox-insensitive variant of a transcription factor. The ability of P. aeruginosa QS transcription factors to integrate information about cell density and cellular redox state shows these transcription factors can fine-tune levels of the gene products they control in response to at least two types of signals or cues.

Can Fibroblasts Be Reprogrammed into Macrophages?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 443-443
Author(s):  
Ru Feng ◽  
Thomas Graf
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Bzip Transcription Factor ◽  
Nih3t3 Cells ◽  
Activation Domains ◽  
Gm Csf ◽  
Infected Cells ◽  
Factor C

Abstract Previous work showed that B cell precursors can be reprogrammed into functional macrophages by the enforced expression of the bZip transcription factor C/EBPalpha. The efficient activation of myelomonocytic genes, such as Mac-1, required the co-operation with endogenous PU.1 (Xie et al. 2004), reflecting the fact that many myelomonocytic genes are regulated by a combination of the two transcription factors. We therefore asked: Is C/EBPa and PU.1 sufficient to convert non-hematopoietic cells into macrophages? To test this, NIH-3T3 cells were co-infected with PU.1-GFP and C/EBPa-hCD4 retrovirusesor control vectors encoding the indicators GFP and hCD4 only. Uninfected cells in the retrovirus treated cultures served as additional controls. Our results showed that ~25% of the PU.1 only infected cells express Mac-1 and that this percentage could be increased ~3 fold by co-expression with C/EBPa. In addition, most cells also expressed CD45 and some expressed F4/80 antigen. The PU.1 infected and the double infected cells, but not the C/EBPa only infected cells, also expressed a number of other myelomonocytic genes as detected by RT-PCR. These included CSF-1R (M-CSFR), GM-CSF Ralpha, Lysozyme, CD32, PYK2 as well as endogenous PU.1. The PU.1 induced reprogramming of fibroblasts required the DNA binding and transcription activation domains, but not the PEST domain of the transcription factor. To test whether the reprogrammed cells have functional macrophage properties, we generated two stable cell lines co-expressing C/EBPa and PU.1 delta PEST (wild type PU.1 is toxic in long-term cultures). These cells were morphologically altered, ingested carboxylated particles, and expressed functional Fc-gamma receptors but were unable to phagocytize antibody coated red blood cells. Remarkably, the two cells lines acquired CSF-1 dependence for growth. In accordance with this finding they exhibited a 10–15 fold reduction of CSF-1 production compared to NIH3T3 cells. The response observed was not restricted to fibroblast cell lines since both embryonic and adult fibroblasts could also be partially reprogrammed by co-infection with PU.1 and C/EBPa in that they expressed Mac-1, CD45, F4/80 and IA MHC antigens. In conclusion, enforced expression of PU.1 and C/EBPa converts fibroblasts into macrophage like cells, indicating that the combination of these two transcription factors is sufficient to regulate the majority of genes that define the myelomonocytic phenotype.

Regulation of the dual-function transcription factor Sp3 by SUMO

2007 ◽  
Vol 35 (6) ◽  
pp. 1393-1396 ◽  
Author(s):  
A. Valin ◽  
G. Gill
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Histone Deacetylases ◽  
Current Data ◽  
Dual Function ◽  
Dependent Manner ◽  
Dual Nature ◽  
Protein Protein Interaction ◽  
Sumo Conjugation ◽  
Specificity Protein

In eukaryotes, gene expression is controlled by a relatively small number of regulators. Post-translational modifications dramatically increase the functional possibilities of those regulators. Modification of many transcription factors and cofactors by SUMO (small ubiquitin-related modifier) correlates, in most cases, with inhibition of transcription. Recent studies suggest a model whereby SUMO conjugation to transcription factors promotes the recruitment of co-repressors through direct protein–protein interaction with the SUMO protein. HDACs (histone deacetylases) are important, but not exclusive, effectors of SUMO-mediated repression. Sp3 (specificity protein 3), a zinc-finger DNA-binding domain transcription factor, has the ability to both activate and repress transcription in a context-dependent manner. SUMOylation regulates the dual nature of Sp3 function. Current data suggest that Sp3 represses transcription in a SUMO-dependent manner but independent of HDACs. Recent studies to identify additional co-repressors associated with SUMO and further investigate regulated activity of Sp3 are providing a deeper understanding of SUMO-dependent mechanisms of transcriptional regulation.

scholarly journals Plasmodium falciparum PfEMP1 Modulates Monocyte/Macrophage Transcription Factor Activation and Cytokine and Chemokine Responses

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
Natália Guimarães Sampaio ◽  
Emily Marie Eriksson ◽  
Louis Schofield
Keyword(s):  
Plasmodium Falciparum ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Basis ◽  
Surface Membrane ◽  
Interleukin 10 ◽  
Immune Gene ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Transcription Factor Activation

ABSTRACTImmunity toPlasmodium falciparummalaria is slow to develop, and it is often asserted that malaria suppresses host immunity, although this is poorly understood and the molecular basis for such activity remains unknown.P. falciparumerythrocyte membrane protein 1 (PfEMP1) is a virulence factor that plays a key role in parasite-host interactions. We investigated the immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to the antiparasitic innate response. RAW macrophages and human primary monocytes were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null parasites. To study the immunomodulatory effect of PfEMP1, transcription factor activation and cytokine and chemokine responses were measured. The level of activation of NF-κB was significantly lower in macrophages stimulated with parasites that express PfEMP1 at the red blood cell surface membrane than in macrophages stimulated with PfEMP1-null parasites. Modulation of additional transcription factors, including CREB, also occurred, resulting in reduced immune gene expression and decreased tumor necrosis factor (TNF) and interleukin-10 (IL-10) release. Similarly, human monocytes released less IL-1β, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and TNF specifically in response to VAR2CSA PfEMP1-containing parasites than in response to PfEMP1-null parasites, suggesting that this immune regulation by PfEMP1 is important in naturally occurring infections. These results indicate that PfEMP1 is an immunomodulatory molecule that affects the activation of a range of transcription factors, dampening cytokine and chemokine responses. Therefore, these findings describe a potential molecular basis for immune suppression byP. falciparum.

scholarly journals Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP–mediated feedforward loop

2021 ◽  
Vol 220 (5) ◽  
Author(s):  
Yujin Lee ◽  
Yoonji Jung ◽  
Dae-Eun Jeong ◽  
Wooseon Hwang ◽  
Seokjin Ham ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Mitogen Activated Protein Kinase ◽  
Bzip Transcription Factor ◽  
Immune Functions ◽  
C Elegans ◽  
Feedforward Loop ◽  
Mitogen Activated Protein ◽  
Living Organisms ◽  
Transcription Factor 1

A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(−) animals. In contrast, p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunity, is only partially required for this rejuvenated immunity. The up-regulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn down-regulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS prevents immune aging via the up-regulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a feedforward mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies against immune aging in humans.

scholarly journals Mutational Analysis of AREA, a Transcriptional Activator Mediating Nitrogen Metabolite Repression in Aspergillus nidulans and a Member of the “Streetwise” GATA Family of Transcription Factors

1998 ◽  
Vol 62 (3) ◽  
pp. 586-596 ◽  
Author(s):  
Richard A. Wilson ◽  
Herbert N. Arst
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Aspergillus Nidulans ◽  
Transcriptional Activator ◽  
Structural Genes ◽  
Gata Factor ◽  
Mutational Change ◽  
Nitrogen Metabolite Repression ◽  
Gata Family

SUMMARY The transcriptional activator AREA is a member of the GATA family of transcription factors and mediates nitrogen metabolite repression in the fungus Aspergillus nidulans. The nutritional versatility of A. nidulans and its amenability to classical and reverse genetic manipulations make the AREA DNA binding domain (DBD) a useful model for analyzing GATA family DBDs, particularly as structures of two AREA-DNA complexes have been determined. The 109 extant mutant forms of the AREA DBD surveyed here constitute one of the highest totals of eukaryotic transcription factor DBD mutants, are discussed in light of the roles of individual residues, and are compared to corresponding mutant sequence changes in other fungal GATA factor DBDs. Other topics include delineation of the DBD using both homology and mutational truncation, use of frameshift reversion to detect regions of tolerance to mutational change, the finding that duplication of the DBD can apparently enhance AREA function, and use of the AREA system to analyze a vertebrate GATA factor DBD. Some major points to emerge from work on the AREA DBD are (i) tolerance to sequence change (with retention of function) is surprisingly great, (ii) mutational changes in a transcription factor can have widely differing, even opposing, effects on expression of different structural genes so that monitoring expression of one or even several structural genes can be insufficient and possibly misleading, and (iii) a mutational change altering local hydrophobic packing and DNA binding target specificity can markedly influence the behavior of mutational changes elsewhere in the DBD.

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