scholarly journals Msn2- and Msn4-Like Transcription Factors Play No Obvious Roles in the Stress Responses of the Fungal Pathogen Candida albicans

2004 ◽  
Vol 3 (5) ◽  
pp. 1111-1123 ◽  
Author(s):  
Susan Nicholls ◽  
Melissa Straffon ◽  
Brice Enjalbert ◽  
André Nantel ◽  
Susan Macaskill ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Stress Responses ◽  
Ectopic Expression ◽  
Heavy Metal Stress ◽  
Luciferase Reporter ◽  
Response Element ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Adverse Environmental Conditions

ABSTRACT In Saccharomyces cerevisiae, the (C2H2)2 zinc finger transcription factors Msn2 and Msn4 play central roles in responses to a range of stresses by activating gene transcription via the stress response element (STRE; CCCCT). The pathogen Candida albicans displays stress responses that are thought to help it survive adverse environmental conditions encountered within its human host. However, these responses differ from those in S. cerevisiae, and hence we predicted that the roles of Msn2- and Msn4-like proteins might have been functionally reassigned in C. albicans. C. albicans has two such proteins: CaMsn4 and Mnl1 (for Msn2- and Msn4-like). CaMSN4, but not MNL1, weakly complemented the inability of an S. cerevisiae msn2 msn4 mutant to activate a STRE-lacZ reporter. Also, the disruption of CaMsn4 and Mnl1 had no discernible effect upon the resistance of C. albicans to heat, osmotic, ethanol, nutrient, oxidative, or heavy-metal stress or upon the stress-activated transcriptome in C. albicans. Furthermore, although Cap1-dependent activation of a Yap response element-luciferase reporter was observed, a STRE reporter was not activated in response to stresses in C. albicans. Ectopic expression of CaMsn4 or Mnl1 did not affect the cellular or molecular responses of C. albicans to stress. Under the conditions tested, the putative activation and DNA binding domains of CaMsn4 did not appear to be functional. These data suggest that CaMsn4 and Mnl1 do not contribute significantly to stress responses in C. albicans. The data are consistent with the idea that stress signaling in this fungus has diverged significantly from that in budding yeast.

scholarly journals Induction of Candida albicans Drug Resistance Genes by Hybrid Zinc Cluster Transcription Factors

2014 ◽  
Vol 59 (1) ◽  
pp. 558-569 ◽  
Author(s):  
Sabrina Schneider ◽  
Joachim Morschhäuser
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Dna Binding ◽  
Target Genes ◽  
Efflux Pumps ◽  
Pathogenic Yeast ◽  
Fluconazole Resistance ◽  
Dna Binding Domains ◽  
Zinc Cluster ◽  
Binding Domains

ABSTRACTThe pathogenic yeastCandida albicanscan develop resistance to azole antifungal drugs by overexpressingERG11, which encodes the drug target, or the multidrug efflux pumpsMDR1andCDR1/CDR2. The constitutive upregulation of these genes is usually caused by gain-of-function mutations in the zinc cluster transcription factors Upc2, Mrr1, and Tac1, respectively. These transcription factors are also required for the induction of their target genes in drug-susceptible strains in the presence of specific stimuli. By swapping the DNA-binding domains of Mrr1, Tac1, and Upc2 we investigated if the hybrid transcription factors could activate their new target genes in response to the same signals. When Tac1 was targeted to theMDR1andERG11promoters, the expression of these genes became inducible by fluphenazine. Similarly,MDR1andCDR2were strongly upregulated by fluconazole when Upc2 was fused to the DNA-binding domains of Mrr1 and Tac1, respectively. In contrast, Mrr1 was unable to promote gene expression in response to benomyl when it was targeted to theCDR2andERG11promoters instead of theMDR1promoter. These results suggest that Tac1 and Upc2 themselves are activated by the inducers fluphenazine and fluconazole, respectively, whereas benomyl does not activate Mrr1 itself but a coregulatory factor that is present at the promoters of Mrr1 target genes. Strains in which the expression levels of Mrr1 and Tac1 target genes were controlled by Upc2 exhibited increased fluconazole resistance, demonstrating that the ability to efficiently upregulate the expression of efflux pumps in the presence of the drug results in enhanced intrinsic fluconazole resistance.

scholarly journals Transcriptional Activation Domains of the Candida albicans Gcn4p and Gal4p Homologs

2006 ◽  
Vol 6 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Mikhail Martchenko ◽  
Anastasia Levitin ◽  
Malcolm Whiteway
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Amino Acid ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Sequence Similarity ◽  
Deletion Analysis ◽  
Dna Binding Domains ◽  
Binding Domains

ABSTRACT Many putative transcription factors in the pathogenic fungus Candida albicans contain sequence similarity to well-defined transcriptional regulators in the budding yeast Saccharomyces cerevisiae, but this sequence similarity is often limited to the DNA binding domains of the molecules. The Gcn4p and Gal4p proteins of Saccharomyces cerevisiae are highly studied and well-understood eukaryotic transcription factors of the basic leucine zipper (Gcn4p) and C6 zinc cluster (Gal4p) families; C. albicans has C. albicans Gcn4p (CaGcn4p) and CaGal4p with DNA binding domains highly similar to their S. cerevisiae counterparts. Deletion analysis of the CaGcn4p protein shows that the N′ terminus is needed for transcriptional activation; an 81-amino-acid region is critical for this function, and this domain can be coupled to a lexA DNA binding module to provide transcription-activating function in a heterologous reporter system. Deletion analysis of the C. albicans Gal4p identifies a C-terminal 73-amino-acid-long transcription-activating domain that also can be transferred to a heterologous reporter construct to direct transcriptional activation. These two transcriptional activation regions show no sequence similarity to the respective domains in their S. cerevisiae homologs, and the two C. albicans transcription-activating domains themselves show little similarity.

scholarly journals Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1

2014 ◽  
Vol 289 (31) ◽  
pp. 21605-21616 ◽  
Author(s):  
Shuo Wang ◽  
Miles H. Linde ◽  
Manoj Munde ◽  
Victor D. Carvalho ◽  
W. David Wilson ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Ets Family ◽  
Site Recognition

Conformational changes in the DNA-binding domains of the ecdysteroid receptor during the formation of a complex with the hsp27 response element

2012 ◽  
Vol 30 (4) ◽  
pp. 379-393 ◽  
Author(s):  
Szymon Pakuła ◽  
Marek Orłowski ◽  
Grzegorz Rymarczyk ◽  
Tomasz Krusiński ◽  
Michał Jakób ◽  
...  
Keyword(s):  
Dna Binding ◽  
Conformational Changes ◽  
Response Element ◽  
Ecdysteroid Receptor ◽  
Dna Binding Domains ◽  
Binding Domains

scholarly journals Dissecting the Repertoire of DNA-Binding Transcription Factors of the Archaeon Pyrococcus furiosus DSM 3638

Life ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 40 ◽  
Author(s):  
Antonia Denis ◽  
Mario Alberto Martínez-Núñez ◽  
Silvia Tenorio-Salgado ◽  
Ernesto Perez-Rueda
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Regulatory Networks ◽  
Pyrococcus Furiosus ◽  
Structural Domain ◽  
Transcriptional Regulatory Networks ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Transcriptional Regulatory ◽  
Cellular Domain

In recent years, there has been a large increase in the amount of experimental evidence for diverse archaeal organisms, and these findings allow for a comprehensive analysis of archaeal genetic organization. However, studies about regulatory mechanisms in this cellular domain are still limited. In this context, we identified a repertoire of 86 DNA-binding transcription factors (TFs) in the archaeon Pyrococcus furiosus DSM 3638, that are clustered into 32 evolutionary families. In structural terms, 45% of these proteins are composed of one structural domain, 41% have two domains, and 14% have three structural domains. The most abundant DNA-binding domain corresponds to the winged helix-turn-helix domain; with few alternative DNA-binding domains. We also identified seven regulons, which represent 13.5% (279 genes) of the total genes in this archaeon. These analyses increase our knowledge about gene regulation in P. furiosus DSM 3638 and provide additional clues for comprehensive modeling of transcriptional regulatory networks in the Archaea cellular domain.

Dimeric transcription factor families: it takes two to tango but who decides on partners and the venue?

1992 ◽  
Vol 103 (1) ◽  
pp. 9-14 ◽  
Author(s):  
K.A. Lee
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Experimental Evidence ◽  
Cdna Cloning ◽  
Transcriptional Activation ◽  
Effector Functions ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Dna Elements

Dimeric transcription factors that bind to DNA are often grouped into families on the basis of dimerization and DNA-binding specificities. cDNA cloning studies have established that members of the same family have structurally related dimerisation and DNA-binding domains but diverge in other regions that are important for transcriptional activation. These features lead to the straightforward suggestion that although all members of a family bind to similar DNA elements, individual members exhibit distinct transcriptional effector functions. This simple view is now supported by experimental evidence from those systems that have proved amenable to study. There are however some largely unaddressed questions that concern the mechanisms that allow family members to go about their business without interference from their highly related siblings. Here I will discuss some insights from studies of the bZIP class of transcription factors.

Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2440-2450 ◽  
Author(s):  
Itaru Matsumura ◽  
Akira Kawasaki ◽  
Hirokazu Tanaka ◽  
Junko Sonoyama ◽  
Sachiko Ezoe ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Cell Lines ◽  
Direct Interaction ◽  
Myeloid Cell ◽  
Megakaryocytic Differentiation ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Endogenous Expression ◽  
Ras Activation

Abstract Lineage-specific transcription factors play crucial roles in the development of hematopoietic cells. In a previous study, it was demonstrated that Ras activation was involved in thrombopoietin-induced megakaryocytic differentiation. In this study, constitutive Ras activation by H-rasG12V evoked megakaryocytic maturation of erythroleukemia cell lines F-36P and K562, but not of myeloid cell line 32D cl3 that lacks GATA-1. However, the introduction of GATA-1 led to reprogramming of 32D cl3 toward erythrocytic/megakaryocytic lineage and enabled it to undergo megakaryocytic differentiation in response to H-rasG12V. In contrast, the overexpression of PU.1 and c-Myb changed the phenotype of K562 from erythroid to myeloid/monocytic lineage and rendered K562 to differentiate into granulocytes and macrophages in response to H-rasG12V, respectively. In GATA-1–transfected 32D cl3, the endogenous expression of PU.1 and c-Myb was easily detectable, but their activities were reduced severely. Endogenous GATA-1 activities were markedly suppressed in PU.1-transfected and c-myb–transfected K562. As for the mechanisms of these reciprocal inhibitions, GATA-1 and PU.1 were found to associate through their DNA-binding domains and to inhibit the respective DNA-binding activities of each other. In addition, c-Myb bound to GATA-1 and inhibited its DNA-binding activities. Mutant GATA-1 and PU.1 that retained their own transcriptional activities but could not inhibit the reciprocal partner were less effective in changing the lineage phenotype of 32D cl3 and K562. These results suggested that GATA-1 activities may be crucial for Ras-mediated megakaryocytic differentiation and that its activities may be regulated by the direct interaction with other lineage-specific transcription factors such as PU.1 and c-Myb.

Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2

2005 ◽  
Vol 289 (2) ◽  
pp. G285-G290 ◽  
Author(s):  
Fuad Alkhoury ◽  
Madhu S. Malo ◽  
Moushumi Mozumder ◽  
Golam Mostafa ◽  
Richard A. Hodin
Keyword(s):  
Alkaline Phosphatase ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Marker Gene ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Intestinal Alkaline Phosphatase ◽  
Human Colon Cancer ◽  
Response Element ◽  
Cis Element

We have examined the role that the caudal-related homeobox transcription factors Cdx1 and Cdx2 play in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase ( IAP). Human colon cancer Caco-2 cells were transiently transfected with Cdx1 and/or Cdx2, and semiquantitative RT-PCR was used to study the effects on IAP mRNA expression. Transfections with a variety of IAP-luciferase reporter constructs were used to identify a Cdx response element located within the human IAP gene promoter. Protein-DNA interactions were examined by EMSA. Results showed that Cdx1 markedly induced IAP mRNA expression, whereas Cdx2 did not, and, in fact, inhibited the Cdx1 effects. Functional analysis revealed that Cdx1 transactivates (fourfold, P < 0.05) the IAP promoter through a novel Cdx response element (GTTTAGA) located between −2369 and −2375 upstream of the translational start site. EMSA showed that both Cdx1 and Cdx2 could bind to the cis element, but in cotransfection experiments, Cdx2 inhibited the Cdx1 effects by ∼50%. Thus we have identified a previously unrecognized interaction between two important gut transcription factors, Cdx1 and Cdx2, in the context of IAP gene regulation. Cdx1 activates the IAP gene via a novel cis element, whereas Cdx2 inhibits the Cdx1 effects.

scholarly journals Activated Notch Inhibits Myogenic Activity of the MADS-Box Transcription Factor Myocyte Enhancer Factor 2C

1999 ◽  
Vol 19 (4) ◽  
pp. 2853-2862 ◽  
Author(s):  
Jeanne Wilson-Rawls ◽  
Jeffery D. Molkentin ◽  
Brian L. Black ◽  
Eric N. Olson
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Notch Signaling Pathway ◽  
Mads Box ◽  
Dna Binding Domains ◽  
Muscle Gene Expression ◽  
Binding Domains ◽  
Myocyte Enhancer Factor ◽  
Bhlh Proteins ◽  
Enhancer Factor

ABSTRACT Skeletal muscle gene expression is dependent on combinatorial associations between members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors and the myocyte enhancer factor 2 (MEF2) family of MADS-box transcription factors. The transmembrane receptor Notch interferes with the muscle-inducing activity of myogenic bHLH proteins, and it has been suggested that this inhibitory activity of Notch is directed at an essential cofactor that recognizes the DNA binding domains of the myogenic bHLH proteins. Given that MEF2 proteins interact with the DNA binding domains of myogenic bHLH factors to cooperatively regulate myogenesis, we investigated whether members of the MEF2 family might serve as targets for the inhibitory effects of Notch on myogenesis. We show that a constitutively activated form of Notch specifically blocks DNA binding by MEF2C, as well as its ability to cooperate with MyoD and myogenin to activate myogenesis. Responsiveness to Notch requires a 12-amino-acid region of MEF2C immediately adjacent to the DNA binding domain that is unique to this MEF2 isoform. Two-hybrid assays and coimmunoprecipitations show that this region of MEF2C interacts directly with the ankyrin repeat region of Notch. These findings reveal a novel mechanism for Notch-mediated inhibition of myogenesis and demonstrate that the Notch signaling pathway can discriminate between different members of the MEF2 family.

scholarly journals Structural Dynamics of the Heterodimerization Between the DNA-Binding Domains from Human FoxP1 and FoP2 Transcription Factors

2021 ◽  
Vol 120 (3) ◽  
pp. 127a
Author(s):  
Exequiel Medina ◽  
Ricardo Coñuecar ◽  
Cesar A. Ramirez-Sarmiento ◽  
Hugo Sanabria ◽  
Jorge Babul
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Structural Dynamics ◽  
Dna Binding Domains ◽  
Binding Domains
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