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EMBO reports 9, 7, 683–689 (2008)
doi:10.1038/embor.2008.73
AOP Published online: 6 June 2008
Prdm1- and Sox6-mediated transcriptional repression specifies muscle fibre type in the zebrafish embryo
EMBO Open
Jonas von Hofsten1, Stone Elworthy1, Michael J Gilchrist2, James C Smith2, Fiona C Wardle2 & Philip W Ingham1
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1 MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
2 Wellcome Trust/Cancer Research-UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Road, Cambridge CB2 1QN, UK
To whom correspondence should be addressed
Philip W Ingham Tel: +44 114 222 2803; Fax: +44 114 276 5413; E-mail: p.w.ingham@sheffield.ac.uk
Received 2 November 2007; Accepted 2 April 2008; Published online 6 June 2008.
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Abstract
The zebrafish u-boot (ubo) gene encodes the transcription factor Prdm1, which is essential for the specification of the primary slow-twitch muscle fibres that derive from adaxial cells. Here, we show that Prdm1 functions by acting as a transcriptional repressor and that slow-twitch-specific muscle gene expression is activated by Prdm1-mediated repression of the transcriptional repressor Sox6. Genes encoding fast-specific isoforms of sarcomeric proteins are ectopically expressed in the adaxial cells of ubotp39 mutant embryos. By using chromatin immunoprecipitation, we show that these are direct targets of Prdm1. Thus, Prdm1 promotes slow-twitch fibre differentiation by acting as a global repressor of fast-fibre-specific genes, as well as by abrogating the repression of slow-fibre-specific genes.
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