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.

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 Association between Hepatocyte Nuclear Factor 6 (HNF-6) and FoxA2 DNA Binding Domains Stimulates FoxA2 Transcriptional Activity but Inhibits HNF-6 DNA Binding

2003 ◽  
Vol 23 (2) ◽  
pp. 437-449 ◽  
Author(s):  
Francisco M. Rausa ◽  
Yongjun Tan ◽  
Robert H. Costa
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Binding Assays ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Coactivator Protein

ABSTRACT In previous studies we used transgenic mice or recombinant adenovirus infection to increase hepatic expression of forkhead box A2 (FoxA2, previously called hepatocyte nuclear factor 3β [HNF-3β]), which caused diminished hepatocyte glycogen levels and reduced expression of glucose homeostasis genes. Because this diminished expression of FoxA2 target genes was associated with reduced levels of the Cut-Homeodomain HNF-6 transcription factor, we conducted the present study to determine whether there is a functional interaction between HNF-6 and FoxA2. Human hepatoma (HepG2) cotransfection assays demonstrated that HNF-6 synergistically stimulated FoxA2 but not FoxA1 or FoxA3 transcriptional activity, and protein-binding assays showed that this protein interaction required the HNF-6 Cut-Homeodomain and FoxA2 winged-helix DNA binding domains. Furthermore, we show that the HNF-6 Cut-Homeodomain sequences were sufficient to synergistically stimulate FoxA2 transcriptional activation by recruiting the p300/CBP coactivator proteins. This was supported by the fact that FoxA2 transcriptional synergy with HNF-6 was dependent on retention of the HNF-6 Cut domain LXXLL sequence, which mediated recruitment of the p300/CBP proteins. Moreover, cotransfection and DNA binding assays demonstrated that increased FoxA2 levels caused a decrease in HNF-6 transcriptional activation of the glucose transporter 2 (Glut-2) promoter by interfering with the binding of HNF-6 to its target DNA sequence. These data suggest that at a FoxA-specific site, HNF-6 serves as a coactivator protein to enhance FoxA2 transcription, whereas at an HNF-6-specific site, FoxA2 represses HNF-6 transcription by inhibiting HNF-6 DNA binding activity. This is the first reported example of a liver-enriched transcription factor (HNF-6) functioning as a coactivator protein to potentiate the transcriptional activity of another liver factor, FoxA2.

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

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.

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.

scholarly journals The Activity of Mammalian brm/SNF2α Is Dependent on a High-Mobility-Group Protein I/Y-Like DNA Binding Domain

1999 ◽  
Vol 19 (6) ◽  
pp. 3931-3939 ◽  
Author(s):  
Brigitte Bourachot ◽  
Moshe Yaniv ◽  
Christian Muchardt
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
High Mobility ◽  
High Mobility Group ◽  
Binding Motif ◽  
High Mobility Group Protein ◽  
Interaction Domain ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Group Protein

ABSTRACT The mammalian SWI-SNF complex is a chromatin-remodelling machinery involved in the modulation of gene expression. Its activity relies on two closely related ATPases known as brm/SNF2α and BRG-1/SNF2β. These two proteins can cooperate with nuclear receptors for transcriptional activation. In addition, they are involved in the control of cell proliferation, most probably by facilitating p105Rb repression of E2F transcriptional activity. In the present study, we have examined the ability of various brm/SNF2α deletion mutants to reverse the transformed phenotype ofras-transformed fibroblasts. Deletions within the p105Rb LXCXE binding motif or the conserved bromodomain had only a moderate effect. On the other hand, a 49-amino-acid segment, rich in lysines and arginines and located immediately downstream of the p105Rb interaction domain, appeared to be essential in this assay. This region was also required for cooperation of brm/SNF2α with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome. The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2α to chromatin.

scholarly journals Specific Pax-6/Microphthalmia Transcription Factor Interactions Involve Their DNA-binding Domains and Inhibit Transcriptional Properties of Both Proteins

2001 ◽  
Vol 276 (31) ◽  
pp. 29330-29337 ◽  
Author(s):  
Nathalie Planque ◽  
Laurence Leconte ◽  
Frédéric M. Coquelle ◽  
Patrick Martin ◽  
Simon Saule
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Microphthalmia Transcription Factor ◽  
Factor Interactions

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.

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