Elf5 13711

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Gene ID: 13711
Gene symbol: elf5
Gene Description: e74-like factor 5
Aliases: ESE-5
Human Ortholog Gene ID: [2001]
Reviewer Judgement: TF Gene
Functional Classification: DNA-Binding: sequence-specific
DBD Protein Group Classification: Winged Helix-Turn-Helix
DBD Protein Group/Family Classification: Winged Helix-Turn-Helix / Ets Domain Family
Homolog Cluster(s): 104156

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[9840936] DNA Binding; Transactivation Mouse Strong A recombinant Elf5 HIS-tag protein of approximately 29 kD, expressed in E. coli and purified by metal-a�nity chromatography, displayed strong binding to consensus ETS binding sites, as analysed by electrophoretic mobility shift assay (EMSA). Elf5 bound the E74 oligonucleotide (containing a GGAA-core), but not to the E74m1 oligonucleotide (which had been mutated to an AGAA-core). The first G-residue of the core has been demonstrated to be a physical point of DNA contact for ETS1, and consequently essential for DNA binding. These results were confirmed through competition analysis. The Elf5-E74 complex was effi�ciently competed by the addition of a 100-fold excess of unlabeled E74 but not by E74m1.

Elf5 also displayed sequence specific binding to diff�erent consensus ETS binding sequences, and did so with diff�erential affi�nity. Competition of the Elf5-E74 complex was achieved by consensus ETS sites from the GM-CSF promoter, erb-B2 promoter, and moloney sarcoma virus (MSV) long terminal repeat (LTR). Elf5 did not appear to be competed at all by an oligonucleotide containing a consensus AP1 binding site.

A reporter construct, containing the chloramphenicol acetyl-transferase (CAT) driven by a minimal TK promoter and multiple ETS/AP1 binding sites (from the polyomavirus enhancer), was co-transfected into COS cells together with an Elf5 expression construct. Analysis of CAT activities revealed that Elf5 expression resulted in an average fivefold transactivation of the reporter. Further, this transactivation was inhibited by addition of an anti-sense Elf5 mRNA expression vector, indicating that Elf5 transactivation was due specifically to the product translated from the sense construct.

Shannan HoSui
[10506207] DNA Binding Human Strong ESE-2 contains an amino-terminal negative regulatory domain that inhibits DNA binding. This was demonstrated by synthesizing full-length ESE-2a and a truncated ESE-2aDelta 42, lacking the first 42 amino acids at the amino terminus, and performing EMSA with the E74 Ets binding site (bound by other Ets family members). Full-length ESE-2a was competitively blocked by both the wild type E74 and mutant E74 oligonucleotides, suggesting that these complexes are nonspecific. In contrast, the truncated ESE-2aDelta 42 protein formed a strong faster migrating protein-DNA complex, which was absent from control lysate and which was competitively blocked by the wild type E74 oligonucleotide but not by the mutant E74 oligonucleotide.

ESE-2 binds to Ets sites in the promoters of several salivary gland- and prostate-specific promoters and to the SPRR2A promoter Ets site. Double-stranded oligos encoding putative Ets binding sites found in the promoters of several salivary gland- and prostrate-specific genes were generated. Relative binding affinity and specificity of the truncated form of ESE-2a for these sites was compared with the affinity for the E74 site by their ability to compete with binding of ESE-2aDelta 42 to the E74 probe.

ESE-2 acts as a transactivator of the PSP promoter. Full-length ESE-2a was inserted into the eukaryotic expression vector pCI and was co-transfected into COS cells together with a pXP2 luciferase reporter gene construct containing two copies of the PSP Ets site inserted upstream of the minimal c-fos promoter Delta 56. Cotransfection with pCI ESE-2a resulted in a 7-fold activation of the PSP promoter Ets site compared with the parental pCI vector, whereas the empty pXP2 vector was not activated by ESE-2a.

Shannan HoSui
Additional Reviewer Comments:
Reviewer: Shannan HoSui

Elf5 is a member of the ETS family of transcription factors. It has been shown to bind specifically to the E74 oligonucleotide which contains the GGAA core. Mutation analysis shows that the first G is required for binding. Elf5 is preferentially expressed in tissues with a high content of epithelial cells. Oettgen et al. suggest that sequence specific DNA binding is modulated by the the first 46 nucleotides of Elf5. Elf5 transactivates promoters from several salivary gland and prostate gland specific genes in luceriferase assays.


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Facts about Elf5 13711RDF feed
Gene description e74-like factor 5  +
Gene id 13,711  +
Gene judgment TF Gene  +
Gene symbol elf5  +, and ESE-5  +
Gene taxonomy DNA-Binding: sequence-specific  +
Homolog cluster 104,156  +
Protein family 1.2 Winged Helix-Turn-Helix/16 Ets Domain Family  +
Protein group 1.2 Winged Helix-Turn-Helix   +
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