The ETS-domain transcription factor family

Sharrocks, A. D.; Brown, Andrew; Ling, Yan; Yates, P.

doi:10.1016/s1357-2725(97)00086-1

Cited by 343 publications

(219 citation statements)

References 77 publications

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“…Indeed, the last residues of the acidic domain are not predicted as being structured . In common with other Ets transcription factors (for review, see Sharrocks et al, 1997) and other PEA3 group members (for review, see , the data that we obtained here indicate that human ETV1a and human ETV1b proteins activate the transcription of a reporter gene driven by the E74 sequence in a similar manner. This suggests that the removal of the end of the conserved acidic domain is not crucial for the activation of the transcription.…”

Section: Discussionsupporting

confidence: 75%

“…The ets genes encode a family of eukaryotic transcription factors that includes more than 30 members from sponges to humans (for a review, see Sharrocks et al, 1997). They have been involved both in tumorigenesis and in a number of developmental processes.…”

Section: Introductionmentioning

confidence: 99%

“…The structural motif of this domain has been determined, so permitting its classi®cation to the winged helix ± turn ± helix superfamily of DNA-binding domains (for review, see Sharrocks et al, 1997). ETS domain transcription factors can be sub-classi®ed primarily because of the high amino acid conservation in their ETS domains and, in addition, in the conservation of other domains generally characterized as transactivating.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

Coutte

Monté

Imai³

et al. 1999

Oncogene

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The Ets transcription factors of the PEA3 group ± E1AF/PEA3, ETV1/ER81 and ERM ± are almost identical in the ETS DNA-binding and the transcriptional acidic domains. To accelerate our understanding of the molecular basis of putative diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1 and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons in more than 90 kbp genomic DNA, and that the classical acceptor and donor splicing sites are present in each junction except for the 5' donor site of intron 9 where GT is replaced by TT. The genomic organization of the ETS and acidic domains in the human ETV1 and mouse ER81 (localized to chromosome 12) genes is similar to that observed in human ERM and human E1AF/PEA3 genes. Moreover, as in human ERM and human E1AF/ PEA3 genes, a ®rst untranslated exon is upstream from the ®rst methionine, and the mouse ER81 gene transcription is regulated by a 1.8 kbp of genomic DNA upstream from this exon. In human, the alternative splicing of the ETV1 gene leads to the presence (ETV1a) or the absence (ETV1b) of exon 5 encoding the Cterminal part of the transcriptional acidic domain, but without a ecting the alpha helix previously described as crucial for transactivation. We demonstrated here that the truncated isoform (human ETV1b) and the fulllength isoform (human ETV1a) bind similarly speci®c DNA Ets binding sites. Moreover, they both activate transcription similarly through the PKA-transduction pathway, so suggesting that this alternative splicing is not crucial for the function of this protein as a transcription factor. The comparison of human ETV1a and human ETV1b expression in the same tissues, such as the adrenal gland or the bladder, showed no clear-cut di erences. Altogether, these data open a new avenue of investigation leading to a better understanding of the functional role of this transcription factor.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

Coutte

Monté

Imai³

et al. 1999

Oncogene

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“…Recognizing that our results suggest complex regulatory mechanisms involving the ets and pointed domains of ELF3, it is also possible that autoregulatory mechanisms may inhibit DNA binding activity as described in Ets-1 where two a-helices located N-terminally to the ets domain and a single Cterminal a-helix act cooperatively to alter DNA binding (Sharrocks et al, 1997). To that end, protein ± protein interactions may modulate autoregulatory mechanisms.…”

Section: Discussionmentioning

confidence: 64%

Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation

et al. 2000

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The ets family of transcription factors comprises many members which contribute to diverse cellular functions that vary depending upon the cell-and tissue-type context. Recently, di erent groups have identi®ed a novel member of the ets family that is epithelial-speci®c. Variably called ESE-1, ERT, jen, ESX, this gene is designated currently as ELF3. In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its e ect on the human keratin 4 gene promoter based upon the role of keratin 4 in early di erentiation of the esophageal squamous epithelium. Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-di erentiation linked SPRR2A promoter. Furthermore, serial deletion constructs of the keratin 4 promoter continued to be suppressed by ELF3, a phenomenon that was only partially rescued by ELF3 ets domain mutants, but completely abrogated by deletion of the ELF3 pointed domain. These results suggest that ELF3 may have dual functions in the transcriptional regulation of genes involved in squamous epithelial di erentiation. One of these functions may not be exclusively mediated through DNA binding in the context of transcriptional suppression of the keratin 4 promoter.

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“…The Ets family contains more than 30 members, which may function as transcription activators, repressors or initiators, and which play important roles during embryogenesis, haematopoiesis and tumour metastasis [10]. Recently, the nucleotide sequence of the proximal promoter region (300 bp) of the murine Dld gene was determined [11].…”

Section: Introductionmentioning

confidence: 99%

Roles of an Ets motif and a novel CACGAC direct repeat in transcription of the murine dihydrolipoamide dehydrogenase (Dld) gene

Yang

Johnson

Patel

1999

Biochemical Journal

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The 5h-flanking region of the murine dihydrolipoamide dehydrogenase (Dld) gene was characterized for its promoter activity. DNase I footprinting analysis of the promoter region (k545 bp to j41 bp) revealed six major protein-binding domains (termed P1 to P6) that were protected by NIH3T3 fibroblast nuclear extracts. Transient transfection assays, using a series of nested deletions of the 2.5 kb 5h-flanking region ligated to the chloramphenicol acetyltransferase reporter gene, identified that the k42-bp to j41-bp region, which harbours the P1, P2, and P3 domains, had minimal transcriptional activity. When the 5h-flanking region was extended from k42 bp to k82 bp, there was an approx. 5-fold increase in promoter activity. To identify further the cis elements involved in transcription of the Dld gene (k82 bp to j41 bp), a series of mutations were introduced into this region and evaluated for functional effects using transient transfection and electrophoretic mobility shift assays. Mutation

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The ETS-domain transcription factor family

Cited by 343 publications

References 77 publications

Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation

Roles of an Ets motif and a novel CACGAC direct repeat in transcription of the murine dihydrolipoamide dehydrogenase (Dld) gene

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