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  • Original Paper
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Molecular characterization of a zebrafish TCF ETS-domain transcription factor

Abstract

The ternary complex factor (TCF) subfamily of ETS-transcription factors represent key nuclear targets of the MAP kinase pathways. Members of this subfamily are classified by the presence of several conserved domains for DNA binding, interaction with SRF, interaction with MAP kinases and transcriptional activation. In this study we have isolated a further member of this subfamily (TCF-1) from zebrafish. The protein product of zebrafish TCF-1 (zTCF-1), shares sequence similarity with the mammalian TCFs in all four conserved domains, with highest overall similarity to SAP-1. Zebrafish TCF-1 is expressed throughout zebrafish embryonic development and exhibits typical TCF DNA binding characteristics, with the B-box being required for interaction with SRF. Of the mammalian TCFs, its DNA binding specificity resembles Elk-1. zTCF-1 is a target for both the growth factor/mitogen-activated and stress-activated MAP kinase cascades in vitro and in vivo. However, differential targeting occurs, with the profile of its activation closely resembling that of mammalian SAP-1. Together, our results demonstrate that the TCFs have been functionally conserved during vertebrate development.

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Acknowledgements

We thank Margaret Bell and Katherine Stewart for excellent technical and secretarial assistance, Bob Liddell for DNA sequencing and oligonucleotide synthesis. We are grateful to members of our laboratories for stimulating discussions and comments on the manuscript. We are also grateful to Alan Whitmarsh and Roger Davis for reagents. This work was supported by grants from the North of England Cancer Research Campaign, Cancer Research Campaign [CRC], the Wellcome Trust, a Newcastle University Research Committee Studentship to LA Brown and a Jeffcock Studentship to A Galanis. AD Sharrocks is a Research Fellow of the Lister Institute of Preventative Medicine.

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Brown, L., Yang, SH., Hair, A. et al. Molecular characterization of a zebrafish TCF ETS-domain transcription factor. Oncogene 18, 7985–7993 (1999). https://doi.org/10.1038/sj.onc.1203197

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