scholarly journals Structural Basis of Alternative DNA Recognition by Maf Transcription Factors

2009 ◽  
Vol 29 (23) ◽  
pp. 6232-6244 ◽  
Author(s):  
Hirofumi Kurokawa ◽  
Hozumi Motohashi ◽  
Shinji Sueno ◽  
Momoko Kimura ◽  
Hiroaki Takagawa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Leucine Zipper ◽  
Dna Recognition ◽  
Coiled Coil ◽  
Structural Basis ◽  
Recognition Mechanism ◽  
Core Motif ◽  
Recognition Element ◽  
Amino Terminal ◽  
Basic Region

ABSTRACT Maf transcription factors constitute a family of the basic region-leucine zipper (bZip) factors and recognize unusually long DNA motifs (13 or 14 bp), termed the Maf recognition element (MARE). The MARE harbors extended GC sequences on each side of its core motif, which is similar to TRE or CRE (7 or 8 bp) recognized by the AP1 and CREB/ATF families, respectively. To ascertain the structural basis governing the acquirement of such unique DNA recognition, we determined the crystal structure of the MafG-DNA complex. Each MafG monomer consists of three helices in which the carboxyl-terminal long helix organizes one DNA-contacting element and one coiled-coil dimer formation element. To our surprise, two well-conserved residues, Arg57 and Asn61 in the basic region, play critical roles in Maf-specific DNA recognition. These two residues show unique side-chain orientations and interact directly with the extended GC bases. Maf-specific residues in the amino-terminal and basic regions appear to indirectly stabilize MARE recognition through DNA backbone phosphate interactions. This study revealed an alternative DNA recognition mechanism of the bZip factors that bestows specific target gene profiles upon Maf homodimers or Maf-containing heterodimers.

scholarly journals DNA binding and dimerization specificities of Basic Zipper transcription factors

2014 ◽  
Vol 70 (a1) ◽  
pp. C1404-C1404
Author(s):  
Vivian Pogenberg ◽  
Larissa Consani-Textor ◽  
Matthias Wilmanns
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Leucine Zipper ◽  
Coiled Coil ◽  
Regulatory Elements ◽  
Biological Data ◽  
Recognition Element ◽  
Eukaryotic Gene ◽  
Complementary Techniques

The ability of basic zipper transcription factors to form homo- or heterodimers provides a paradigm for combinatorial control of eukaryotic gene expression. In a first study, we clarified the specificity of the MIcrophthalmia-associated Transcription Factor [1]. To achieve this, we solved three crystal structures: two structures of MITF in complex with DNA duplexes encompassing two different target motifs (E-box and M-box) and one APO-structure. We then analyzed interactions between these DNA elements and several MITF mutants with documented mice phenotypes, using complementary techniques. The comparison of these experiments together with available biological data reveals the particular mechanism of DNA recognition by MITF. Moreover we demonstrated how a shift in the leucine zipper register limits the choice of the homotypic dimerization partner among the other b-HLH-Zip transcription factors. In a second study, we wondered how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements [2]. In this respect, the hematopoietic b-Zip transcription factor MafB, is a good model, since it has the ability to form homo- and heterodimers with a few other transcription factors. We first determined two high-resolution structures of MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element (MARE). The two structures revealed several unexpected and specific coiled coil interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them indeed showed a strong preference for MafB/c-Fos heterodimerization. In addition this variant enabled a selection of heterodimer- favoring over homodimer-specific MARE variants, demonstrating that protein/protein and protein/DNA interactions are interconnected. Our data provide a new concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.

scholarly journals Domain swapping reveals the modular nature of Fos, Jun, and CREB proteins.

1990 ◽  
Vol 10 (9) ◽  
pp. 4565-4573 ◽  
Author(s):  
L J Ransone ◽  
P Wamsley ◽  
K L Morley ◽  
I M Verma
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Chimeric Protein ◽  
Domain Swapping ◽  
Amino Terminus ◽  
Protein Protein Interactions ◽  
Amino Terminal ◽  
Nih 3T3 ◽  
Basic Region

The products of the Jun and Fos proto-oncogenes form a heterodimer that binds to and activates transcription from 12-O-tetradecanoylphorbol-13-acetate-responsive promoter elements (TGACTCA) and AP-1-binding sites (TGACATCA). These two proteins belong to a family of related transcription factors which contain similar domains required for protein dimerization and DNA binding but display different protein and DNA binding specificities. The basic region, required for DNA binding, is followed by a leucine zipper structure, a domain that mediates protein-protein interactions. To assess the role of these two domains in three related proteins, Fos, Jun, and CREB, we carried out extensive domain-swapping analysis. We found that (i) dimers formed by two Jun leucine zipper-containing proteins were unable to bind DNA as efficiently as a Fos-Jun combination, regardless of the source of the basic region; (ii) the Fos leucine zipper was unable to form either homo- or heterodimers with a chimeric protein containing a Fos leucine zipper; (iii) the Fos basic region was capable of binding to an AP-1 site; (iv) replacement of the Jun amino terminus with that of CREB had little effect on dimerization, whereas replacement with the amino terminus of Fos disrupted both protein-protein and protein-DNA interactions; (v) changes in relative affinities of the Fos and Jun basic regions for the AP-1 element were dependent on the secondary contributions of amino-terminal residues; and (vi) the Fos-Jun chimeric constructs cooperated in transcriptional transactivation of the Jun promoter in NIH 3T3 cells.

DNA recognition by nuclear receptors

2004 ◽  
Vol 40 ◽  
pp. 59-72 ◽  
Author(s):  
Frank Claessens ◽  
Daniel T Gewirth
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Nuclear Receptors ◽  
Dna Sequences ◽  
Dna Recognition ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Core Motif ◽  
Response Elements ◽  
Sequence Recognition

The nuclear receptors constitute a large family of ligand-inducible transcription factors. The control of many genetic pathways requires the assembly of these nuclear receptors in defined transcription-activating complexes within control regions of ligand-responsive genes. An essential step is the interaction of the receptors with specific DNA sequences, called hormone-response elements (HREs). These response elements position the receptors, and the complexes recruited by them, close to the genes of which transcription is affected. HREs are bipartite elements that are composed of two hexameric core half-site motifs. The identity of the response elements resides in three features: the nucleotide sequence of the two core motif half-sites, the number of base pairs separating them and the relative orientation of the motifs. The DNA-binding domains of nuclear receptors consist of two zinc-nucleated modules and a C-terminal extension. Residues in the first module determine the specificity of the DNA recognition, while residues in the second module are involved in dimerization. Indeed, nuclear receptors bind to their HREs as either homodimers or heterodimers. Depending on the type of receptor, the C-terminal extension plays a role in sequence recognition, dimerization, or both. The DNA-binding domain is furthermore involved in several other functions including nuclear localization, and interaction with transcription factors and co-activators. It is also the target of post-translational modifications. The DNA-binding domain therefore plays a central role, not only in the correct binding of the receptors to the target genes, but also in the control of other steps of the action mechanism of nuclear receptors.

Domain swapping reveals the modular nature of Fos, Jun, and CREB proteins

1990 ◽  
Vol 10 (9) ◽  
pp. 4565-4573
Author(s):  
L J Ransone ◽  
P Wamsley ◽  
K L Morley ◽  
I M Verma
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Chimeric Protein ◽  
Domain Swapping ◽  
Amino Terminus ◽  
Protein Protein Interactions ◽  
Amino Terminal ◽  
Nih 3T3 ◽  
Basic Region

The products of the Jun and Fos proto-oncogenes form a heterodimer that binds to and activates transcription from 12-O-tetradecanoylphorbol-13-acetate-responsive promoter elements (TGACTCA) and AP-1-binding sites (TGACATCA). These two proteins belong to a family of related transcription factors which contain similar domains required for protein dimerization and DNA binding but display different protein and DNA binding specificities. The basic region, required for DNA binding, is followed by a leucine zipper structure, a domain that mediates protein-protein interactions. To assess the role of these two domains in three related proteins, Fos, Jun, and CREB, we carried out extensive domain-swapping analysis. We found that (i) dimers formed by two Jun leucine zipper-containing proteins were unable to bind DNA as efficiently as a Fos-Jun combination, regardless of the source of the basic region; (ii) the Fos leucine zipper was unable to form either homo- or heterodimers with a chimeric protein containing a Fos leucine zipper; (iii) the Fos basic region was capable of binding to an AP-1 site; (iv) replacement of the Jun amino terminus with that of CREB had little effect on dimerization, whereas replacement with the amino terminus of Fos disrupted both protein-protein and protein-DNA interactions; (v) changes in relative affinities of the Fos and Jun basic regions for the AP-1 element were dependent on the secondary contributions of amino-terminal residues; and (vi) the Fos-Jun chimeric constructs cooperated in transcriptional transactivation of the Jun promoter in NIH 3T3 cells.

scholarly journals Analysis of TabZIP15 transcription factor from Trichoderma asperellum ACCC30536 and its function under pathogenic toxin stress

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zeyang Yu ◽  
Zhiying Wang ◽  
Yuzhou Zhang ◽  
Yucheng Wang ◽  
Zhihua Liu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Leucine Zipper ◽  
Differential Expression Analysis ◽  
Trichoderma Asperellum ◽  
Nutrient Competition ◽  
Gene Encoding ◽  
Cytospora Chrysosperma ◽  
Minimal Media ◽  
Basic Region

Abstract The TabZIP15 gene encoding a 396 amino acid (aa) polypeptide in the fungus Trichoderma asperellum ACCC30536 was cloned and characterised. The protein includes a basic region motif (NR-x2-QR-x2-R) and has a pillar-like structure. The 25 basic region/leucine zipper transcription factors (TFs) identified in the T. asperellum genome were divided into YAP (14 TFs), ATF2 (5), GCN4 (2), Zip1 (2), BRLZ (1) and u1 (1) subfamilies based on conserved domains. T. asperellum was cultured in minimal media (MM) control, C-Hungry and N-Hungry medium (to simulate nutrient competition and interaction with pathogens, respectively), and differential expression analysis showed that 14 TabZIP genes (including TabZIP15) were significantly altered under both conditions; TabZIP23 responded strongly to N-Hungry media and TabZIP24 responded strongly to C-Hungry media. However, only YAP genes TabZIP15, TabZIP12 and TabZIP2 were significantly upregulated under both conditions, and expression levels of TabZIP15 were highest. T. asperellum was also cultured in the presence of five fungal pathogenic toxins, and RT-qPCR results showed that TabZIP15 was significantly upregulated in four of the five toxin stress conditions (MM + Rhizoctonia solani, MM + Fusarium oxysporum, MM + Alternaria alternata and MM + Cytospora chrysosperma).

scholarly journals Redox-mediated Mechanisms Regulate DNA Binding Activity of the G-group of Basic Region Leucine Zipper (bZIP) Transcription Factors inArabidopsis

2012 ◽  
Vol 287 (33) ◽  
pp. 27510-27525 ◽  
Author(s):  
Jehad Shaikhali ◽  
Louise Norén ◽  
Juan de Dios Barajas-López ◽  
Vaibhav Srivastava ◽  
Janine König ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Leucine Zipper ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Bzip Transcription Factors ◽  
Basic Region
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