Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor.

The maf oncogene encodes a bZip nuclear protein which recognizes sequences related to an AP-1 site either as a homodimer or as heterodimers with Fos and Jun. We describe here a novel maf-related gene, mafG, which shows extensive homology with two other maf-related genes, mafK and mafF. These three maf-related genes encode small basic-leucine zipper proteins lacking the trans-activator domain of v-Maf. Bacterially expressed small Maf proteins bind to DNA as homodimers with a sequence recognition profile that is virtually identical to that of v-Maf. As we have previously described, the three small Maf proteins also dimerize with the large subunit of NF-E2 (p45) to form an erythroid cell-specific transcription factor, NF-E2, which has distinct DNA-binding specificity. This study shows that the small Maf proteins can also dimerize among themselves and with Fos and a newly identified p45-related molecule (Ech) but not with v-Maf or Jun. Although the small Maf proteins preferentially recognize the consensus NF-E2 sequence as heterodimers with either NF-E2 p45, Ech, or Fos, these heterodimers seemed to be different in their transactivation potentials. Coexpression of Fos and small Mafs could not activate a promoter with tandem repeats of the NF-E2 site. These results raise the possibility that tissue-specific gene expression and differentiation of erythroid cells are regulated by competition among Fos, NF-E2 p45, and Ech for small Maf proteins and for binding sites.

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DNA-binding specificity of the PAR basic leucine zipper protein VBP partially overlaps those of the C/EBP and CREB/ATF families and is influenced by domains that flank the core basic region.

Molecular and Cellular Biology ◽

10.1128/mcb.15.4.1923 ◽

1995 ◽

Vol 15 (4) ◽

pp. 1923-1932 ◽

Cited By ~ 38

Author(s):

N B Haas ◽

C A Cantwell ◽

P F Johnson ◽

J B Burch

Keyword(s):

Binding Sites ◽

Leucine Zipper ◽

Affinity Binding ◽

Basic Leucine Zipper ◽

High Affinity Binding ◽

High Affinity ◽

The Core ◽

Dna Binding Specificity ◽

Basic Region ◽

Half Site

The PAR subfamily of basic leucine zipper (bZIP) factors comprises three proteins (VBP/TEF, DBP, and HLF) that have conserved basic regions flanked by proline- and acidic-amino-acid-rich (PAR) domains and functionally compatible leucine zipper dimerization domains. We show that VBP preferentially binds to sequences that consist of abutted GTAAY half-sites (which we refer to as PAR sites) as well as to sequences that contain either a C/EBP half-site (GCAAT) or a CREB/ATF half-site (GTCAT) in place of one of the PAR half-sites. Since the sequences that we describe as PAR sites and PAR-CREB/ATF chimeric sites, respectively, were both previously described as high-affinity binding sites for the E4BP4 transcriptional repressor, we infer that these sequences may be targets for positive and negative regulation. Similarly, since the sequences that we describe as PAR-C/EBP and PAR-CREB/ATF chimeric sites are known to be high-affinity binding sites for C/EBP and CREB/ATF factors, respectively, we infer that these sites may each be targets for multiple subfamilies of bZIP factors. To gain insights regarding the molecular basis for the binding-site specificity of PAR factors, we also carried out an extensive mutational analysis of VBP. By substituting five amino acid residues that differ between the Drosophila giant bZIP factor and the vertebrate PAR bZIP factors, we show that the fork region, which bridges the basic and leucine zipper domains, contributes to half-site sequence specificity. In addition, we report that at least two domains amino terminal to the core basic region are required for VBP to bind to the full spectrum of PAR target sites. Thus, whereas direct base contacts may be restricted to basic-region residues (as indicated by GCN4-DNA crystal structures), several other domains also influence the DNA-binding specificity of PAR bZIP proteins.

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A PAR domain transcription factor is involved in the expression from a hematopoietic-specific promoter for the human LMO2 gene

Blood ◽

10.1182/blood-2002-09-2702 ◽

2003 ◽

Vol 101 (12) ◽

pp. 4757-4764 ◽

Cited By ~ 24

Author(s):

Scott C. Crable ◽

Kathleen P. Anderson

Keyword(s):

Transcription Factor ◽

Protein Interactions ◽

Leucine Zipper ◽

Cell Lineage ◽

Erythroid Cell ◽

Protein Protein Interactions ◽

Consensus Binding Site ◽

Basic Leucine Zipper ◽

Specific Expression ◽

Dna Binding Factors

AbstractThe transcription factor LMO2 is believed to exert its effect through the formation of protein-protein interactions with other DNA-binding factors such as GATA-1 and TAL1. Although LMO2 has been shown to be critical for the formation of the erythroid cell lineage, the gene is also expressed in a number of nonerythroid tissues. In this report, we demonstrate that the more distal of the 2 promoters for the LMO2 gene is highly restricted in its pattern of expression, directing the hematopoietic-specific expression of this gene. Deletion and mutation analyses have identified a critical cis element in the first untranslated exon of the gene. This element is a consensus-binding site for a small family of basic leucine zipper proteins containing a proline and acidic amino acid–rich (PAR) domain. Although all 3 members of this family are produced in erythroid cells, only 2 of these proteins, thyrotroph embryonic factor and hepatic leukemia factor, can activate transcription from this LMO2 promoter element. These findings represent a novel mechanism in erythroid gene regulation because PAR proteins have not previously been implicated in this process.

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Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.90.23.11371 ◽

1993 ◽

Vol 90 (23) ◽

pp. 11371-11375 ◽

Cited By ~ 231

Author(s):

J Y Chan ◽

X L Han ◽

Y W Kan

Keyword(s):

Transcription Factor ◽

Binding Sites ◽

Leucine Zipper ◽

Genetic Selection ◽

Yeast Cells ◽

Binding Motif ◽

Related Factor ◽

Transcriptional Activators ◽

Basic Leucine Zipper ◽

Related Transcription Factor

We have devised a complementation assay in yeast to clone mammalian transcriptional activators and have used it to identify a human basic leucine-zipper transcription factor that we have designated Nrf1 for NF-E2-related factor 1. Nrf1 potentially encodes a 742-aa protein and displays marked homology to the mouse and human NF-E2 transcription factors. Nrf1 activates transcription via NF-E2 binding sites in yeast cells. The ubiquitous expression pattern of Nrf1 and the range of promoters containing the NF-E2 binding motif suggest that this gene may play a role in the regulation of heme synthesis and ferritin genes.

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Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF.

Molecular and Cellular Biology ◽

10.1128/mcb.15.5.2437 ◽

1995 ◽

Vol 15 (5) ◽

pp. 2437-2447 ◽

Cited By ~ 344

Author(s):

M Merika ◽

S H Orkin

Keyword(s):

Transcription Factor ◽

Binding Sites ◽

Close Association ◽

Regulatory Elements ◽

Erythroid Cell ◽

Specific Gene ◽

Specific Expression ◽

Locus Control Regions ◽

Control Regions

An unresolved aspect of current understanding of erythroid cell-specific gene expression relates to how a limited number of transcriptional factors cooperate to direct high-level expression mediated by cis-regulatory elements separated over large distances within globin loci. In this report, we provide evidence that GATA-1, the major erythroid transcription factor, activates transcription in a synergistic fashion with two Krüppel family factors, the ubiquitous protein Sp1 and the erythroid-restricted factor EKLF (erythroid Krüppel-like factor), which recognize GC and/or GT/CACC motifs. Binding sites for both GATA-1 and these Krüppel proteins (especially Sp1) are found in close association in the promoters and enhancers of numerous erythroid cell-expressed genes and appear to cooperate in directing their expression. We have shown that GATA-1 interacts physically with Sp1 and EKLF and that interactions are mediated through their respective DNA-binding domains. Moreover, we show that GATA-1 and Sp1 synergize from a distance in constructs designed to mimic the architecture of globin locus control regions and downstream globin promoters. Finally, the formation of GATA-1-SP1 complexes was demonstrated in vivo by the ability of Sp1 to recruit GATA-1 to a promoter in the absence of GATA-binding sites. These experiments provide the first evidence for functionally important protein-protein interactions involved in erythroid cell-specific expression and suggest a mechanism by which DNA loops between locus control regions and globin promoters (or enhancers) might be formed or stabilized.

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Faculty Opinions recommendation of The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1163876.625706 ◽

2009 ◽

Author(s):

Eric Vivier

Keyword(s):

Transcription Factor ◽

Natural Killer Cell ◽

Natural Killer ◽

Leucine Zipper ◽

Killer Cell ◽

Cell Development ◽

Basic Leucine Zipper

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Faculty Opinions recommendation of The basic leucine zipper domain transcription factor Atf1 directly controls Cdc13 expression and regulates mitotic entry independently of Wee1 and Cdc25 in Schizosaccharomyces pombe.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718349320.793494863 ◽

2014 ◽

Author(s):

Christopher McInerny

Keyword(s):

Transcription Factor ◽

Schizosaccharomyces Pombe ◽

Leucine Zipper ◽

Basic Leucine Zipper ◽

Mitotic Entry ◽

Leucine Zipper Domain

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Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

Nucleic Acids Research ◽

10.1093/nar/gkab185 ◽

2021 ◽

Vol 49 (7) ◽

pp. 3856-3875

Author(s):

Marina Kulik ◽

Melissa Bothe ◽

Gözde Kibar ◽

Alisa Fuchs ◽

Stefanie Schöne ◽

...

Keyword(s):

Gene Regulation ◽

Transcription Factor ◽

Dna Binding ◽

Receptor Binding ◽

Binding Sites ◽

Specific Gene ◽

Functional Diversification ◽

Enhancer Activity ◽

Sequence Composition

Abstract The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied them in an equivalent cellular context. Analysis of chromatin and sequence suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the result of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.

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A Pivotal Role of the Basic Leucine Zipper Transcription Factor bZIP53 in the Regulation of Arabidopsis Seed Maturation Gene Expression Based on Heterodimerization and Protein Complex Formation

The Plant Cell ◽

10.1105/tpc.108.062968 ◽

2009 ◽

Vol 21 (6) ◽

pp. 1747-1761 ◽

Cited By ~ 109

Author(s):

Rosario Alonso ◽

Luis Oñate-Sánchez ◽

Fridtjof Weltmeier ◽

Andrea Ehlert ◽

Isabel Diaz ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Complex Formation ◽

Protein Complex ◽

Leucine Zipper ◽

Pivotal Role ◽

Basic Leucine Zipper ◽

Arabidopsis Seed ◽

Protein Complex Formation

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Induction of metallothionein I by phenolic antioxidants requires metal-activated transcription factor 1 (MTF-1) and zinc

Biochemical Journal ◽

10.1042/bj20031677 ◽

2004 ◽

Vol 380 (3) ◽

pp. 695-703 ◽

Cited By ~ 39

Author(s):

Yongyi BI ◽

Richard D. PALMITER ◽

Kristi M. WOOD ◽

Qiang MA

Keyword(s):

Transcription Factor ◽

Phase Ii ◽

Leucine Zipper ◽

Gene Promoter ◽

Phenolic Antioxidants ◽

Related Factor ◽

Basic Leucine Zipper ◽

Free Zinc ◽

Genes Encoding ◽

Transcription Factor 1

Phenolic antioxidants, such as tBHQ [2,5-di-(t-butyl)-1,4-hydroquinone], induce Mt1 (metallothionein 1) gene expression and accumulation of MT protein. Induction of Mt1 mRNA does not depend on protein synthesis, and correlates with oxidation–reduction functions of the antioxidants. In the present study, we analysed the biochemical pathway of the induction. Induction depends on the presence of MTF-1 (metal-activated transcription factor 1), a transcription factor that is required for metal-induced transcription of Mt1, but does not require nuclear factor erythroid 2-related factor 2, a tBHQ-activated CNC bZip (cap ‘n’ collar basic leucine zipper) protein, that is responsible for regulating genes encoding phase II drug-metabolizing enzymes. Moreover, tBHQ induces the expression of MRE-βGeo, a reporter gene driven by five metal response elements that constitute an optimal MTF-1 binding site. Reconstitution of Mtf1-null cells with MTF-1 restores induction by both zinc and tBHQ. Unlike activation of phase II genes by tBHQ, induction of Mt1 expression does not occur in the presence of EDTA, when cells are cultured in zinc-depleted medium, or in cells with reduced intracellular ‘free’ zinc due to overexpression of ZnT1, a zinc-efflux transporter, indicating that induction requires zinc. In addition, fluorescence imaging reveals that tBHQ increases cytoplasmic free zinc concentration by mobilizing intracellular zinc pools. These findings establish that phenolic antioxidants activate Mt1 transcription by a zinc-dependent mechanism, which involves MTF-1 binding to metal regulator elements in the Mt1 gene promoter.

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