Prdm1- and Sox6-mediated transcriptional repression specifies muscle fibre type in the zebrafish embryo.
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 ubo(tp39) 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.
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Jonas
J
von Hofsten
Stone
S
Elworthy
Michael J
MJ
Gilchrist
James C
JC
Smith
Fiona C
FC
Wardle
Philip W
PW
Ingham
D000818:Animals; D001665:Binding Sites; D024722:Cardiac Myosins / Q000235:genetics; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology; D009154:Mutation / Q000235:genetics; D018994:Myosin Light Chains / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018994:Myosin Light Chains; D009687:Nuclear Proteins; D012097:Repressor Proteins; C531459:Sox6 protein, zebrafish; D029961:Zebrafish Proteins; C107184:myosin light chain 2; D000074462:Positive Regulatory Domain I-Binding Factor 1; C513257:prdm1a protein, zebrafish; D024722:Cardiac Myosins