bZIP Transcription Factor Family Research Articles

Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization.

A family of human genes encoding basic-leucine zipper (bZIP) transcription factors, p45-NF-E2, Nrf1 and Nrf2, have been isolated independently. Whereas the encoded proteins of the three genes share highly conserved regions distinct from other bZIP families such as Jun or Fos, remaining regions diverged considerably from each other. Chromosomal localization by fluorescence in situ hybridization demonstrates that these genes are non-syntenic. p45-NF-E2 mapped to chromosome 12q13.1-13.3, whereas Nrf1 and 2 mapped to 17q21.3 and 2q31, respectively. However, these three genes were probably derived from a single ancestor by chromosomal duplication as other genes that also map in these regions are related to one another.

Isolation and Characterization of STGA1, a Member of the TGA1 Family of bZIP Transcription Factors from Soybean

Isolation and Characterization of STGA1, a Member of the TGA1 Family of bZIP Transcription Factors from Soybean

C-Jun represses transcription of the human chorionic gonadotropin alpha and beta genes through distinct types of CREs.

Chorionic gonadotropin (CG) is a heterodimeric placental hormone encoded by separate alpha and beta subunit genes that is essential for the maintenance of pregnancy. The production of CG is stimulated by DNA synthesis inhibitors and by cAMP. The present study demonstrates that the proto-oncogene c-jun represses transcription of the human CG alpha and CG beta promoters. c-Jun repressed the CG alpha promoter through a canonical cAMP response element (CRE) that is known to bind c-Jun and other members of the B-Zip transcription factor family. In the CG beta promoter, two adjacent sites, CRE1 (-299 to -289) and CRE2 (-240 to -219), conveyed cAMP responsiveness via sequences that are distinct from the canonical element, TGACGTCA. Mutations within CG beta CRE1 or CRE2 reduced or abolished, respectively, c-Jun-mediated repression. Although the CG beta CREs do not contain consensus sequences previously described to bind c-Jun, CRE2 bound c-Jun and c-Fos in electrophoretic mobility shift assays. Supershift assays, using anti-JUN antibody, demonstrated that Jun formed part of the native complex that binds the CRE2 in JEG-3 cells. A series of c-Jun mutants were used to analyze the transcription factor domains required for repression of the CG subunit promoters. The DNA binding and leucine zipper domains of c-Jun as well as the amino terminus, were required for repression of both subunit promoters. Thus, both the CG alpha and CG beta genes are repressed by c-Jun through promoter regions that convey cAMP-induced transcription, although these DNA sequences are unrelated.

Genesis of an organ: molecular analysis of the pha-1 gene

The organisation of organ formation is still an unsolved problem. Mutations in the zygotic lethal gene pha-1 affect a late step during organ development in the nematode C. elegans. In mutant embryos all tissues in the pharynx fail to undergo terminal differentiation and morphogenesis. The expression of an early differentiation marker in pharyngeal muscle precursors is not impaired in mutant embryos, which suggests that pharynx cells still acquire their identity. Therefore the gene defines an organ-specific terminal differentiation function. We cloned and sequenced the pha-1 gene and found that the deduced protein sequence contains features characteristic of the bZIP family of transcription factors. During embryogenesis a transgenic pha-1 reporter construct is expressed transiently in all pharynx precursor cells at the time when these cells become restricted to form the pharynx organ. A mosaic analysis of the requirement of pha-1 activity during pharynx formation is consistent with the notion that pha-1 acts cell-autonomously in all cells of the pharynx primordium. The data suggest that pha-1 initiates and coordinates programs required for cytodifferentiation and morphogenesis in all cell types of the entire organ on the transcriptional level. We propose that organs are independent developmental units whose identity is reflected on the gene regulatory level.

TGA3 is a distinct member of the TGA family of bZIP transcription factors in Arabidopsis thaliana.

TGA1a is a well-characterized transcription factor that may mediate the root-specific and auxin-responsive expression of some plant genes. In tobacco, Southern blot and genomic cloning analyses have shown that TGA1a consists of at least four closely related genes. Since TGA1a belongs to the bZIP class of transcriptional factors, the protein products of the tobacco TGA1a family are likely to form hetero-dimers with each other in addition to the homo-dimers. In order to find a model plant system that may have less genomic complexity, we have now characterized a TGA1a-related gene (TGA3) from Arabidopsis thaliana. Southern blot analyses at high stringency suggest that Arabidopsis contains only one copy of TGA3 per haploid genome. However, low stringency Southern blot analyses with homologous and heterologous probes suggest that there is a multigene family of TGA1a-related genes present in Arabidopsis, of which TGA1, TGA2 and TGA3 are members. Although these gene members share a highly conserved bZIP region, they are not genes with high homologies at the nucleotide level. Similar to TGA1a of tobacco, TGA3 is most highly expressed in root tissues and recombinant TGA3 protein shows similar DNA-binding site specificity to that of TGA1a in vitro. Comparison of the genomic organization between TGA3 and the tobacco homologue PG13 reveals striking conservation in the sizes and positions of exons and introns in the region surrounding the bZIP domain.

Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters.

The prototype mammalian proprotein processing enzyme furin is shown to be encoded by three distinct FUR mRNA isoforms which differ only in their 5'-untranslated regions. By primer extension analysis, the transcription start sites of the three mRNA isoforms were defined. The genomic regions located immediately upstream of the three alternative transcriptional start sites were shown to possess promoter activity in transfection experiments using the luciferase encoding gene as reporter. In a liver cell line, the P1 promoter appeared to be the strongest; in a lung cell line, the P1A promoter. Human FUR promoter P1 but not P1A or P1B was transactivated by transcription factor C/EBP beta. Other members of this family of bZIP transcription factors, C/EBP alpha and C/EBP delta, were not able to transactivate the P1 promoter. Promoter P1A and P1B have characteristics of promoters of housekeeping genes. They lack TATA or CAAT boxes upstream of the transcription start site but are very GC-rich and contain several SP1 sites. Promoter P1, on the other hand, has a TATA box in the proximal promoter region. In electromobility shift assays and DNase I footprinting analysis, transcription factor SP1 was found to bind to the proximal region of the P1 promoter. Altogether, our results indicate that expression of the human FUR gene is directed by alternative promoters, housekeeping (GC-rich) as well as regulated (TATA-containing) promoters, suggesting that their differential use may be a mechanism to modulate levels of the furin enzyme.

Translation start site multiplicity of the CCAAT/enhancer binding protein alpha mRNA is dictated by a small 5' open reading frame.

The CCAAT/enhancer binding proteins (C/EBP) alpha and beta of the bZIP family of transcription factors each occur as multiple forms due to translation initiation at different in-frame AUG codons from the same messenger RNA. The C/EBP alpha mRNAs of chicken, rat and Xenopus all contain a small 5' open reading frame (5'ORF) whose size (18 nucleotides) and distance (seven nucleotides) to the C/EBP alpha cistron has been conserved in vertebrate evolution. The present studies shows that the small 5'ORF is crucial to the leaky scanning mechanism of ribosomes causing a fraction of them to ignore the first C/EBP alpha AUG codon and to start at internal AUGs. Our data challenge the view that translational start site multiplicity is mainly governed by the sequence context of the potential initiation codons. Western analysis showed that the two major chicken C/EBP alpha translation products, the full-length cC/EBP alpha-42 which acts a trans-activator in liver and the N-terminally truncated cC/EBP alpha-29 which lacks transcription activation potential, occur in a fixed ratio which is similar in different expressing tissues, like liver, lung and small intestine. The presence of a similar, thusfar unnoticed, small ORF 5' to the major initiation codon of C/EBP beta mRNA suggests that start site multiplicity from this mRNA may be governed by the same mechanism.

Transcriptional repression by a novel member of the bZIP family of transcription factors.

We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors.

Transcriptional repression by a novel member of the bZIP family of transcription factors.

We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors.

Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta.

Alterations in intracellular calcium levels activate several signal transduction pathways resulting in distinct patterns of gene expression. Here, a pathway for calcium-mediated signals is demonstrated that involves C/EBP beta, a member of the bZip family of transcription factors. In pituitary cells C/EBP beta was phosphorylated in response to increased intracellular calcium concentrations as a consequence of the activation of a calcium-calmodulin-dependent protein kinase. Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.

Updating structure-function relationships in the bZip family of transcription factors: Current Opinion in Structural Biology 1992, 2:116…-123

Transcriptional control is modulated by the interaction of various transcription factors both with DNA and with other proteins. Dimer formation is an important feature of the interaction of these proteins with DNA. The leucine zipper motif defines a novel dimerization interface formed by the supercoiling of two α-helices to form a parallel coiled coil. The bZip family of leucine-zipper proteins has an adjacent basic region that is amino-terminal to the coiled-coil subdomain and which is responsible for sequence-specific DNA binding. Sequence specificity, binding affinity and regulatory protein-protein interactions appear to be modulated by homodimer-heterodimer equilibria both within and between subclasses of the bZip family.