XinGang WANG1, Yosuke ONO1, Swee Chuan TAN1, Ruth Jin Fen CHAI1,4, Caroline PARKIN1,3, Philip W INGHAM1,2.
1 - Institute of Molecular and Cell Biology, Singapore.
2 - Department of Biological Sciences, National University of Singapore.
3 - MRC Centre for Developmental and Biomedical Genetics, Firth Court, Western Bank, Sheffield, S10 2TN, UK
4 - School of Anatomy and Human Biology, The University of Western Australia, Perth 6009, WA, Australia
Published in Development, 31 August 2011 (Epub ahead of print.)
Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle fibre-type
specification. In zebrafish, sox6 transcription is repressed in slow-twitch progenitors by
the Prdm1a transcription factor. Here we identify sox6 cis-regulatory sequences that drive
fast-twitch-specific expression in a Prdm1a–dependent manner. We show that sox6
transcription subsequently becomes derepressed in slow-twitch fibres whereas Sox6 protein remains restricted to fast-twitch fibres. We find that translational repression of
sox6 is mediated by miR-499, the slow-twitch-specific expression of which is in turn
controlled by Prdm 1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.