Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Development. 2011 Oct;138(20):4399-404. doi: 10.1242/dev.070516. Epub 2011 Aug 31.
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 Prdm1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.
Sox6 被认为在脊椎动物骨骼肌纤维类型特化中发挥保守作用。在斑马鱼中，sox6 的转录受到 Prdm1a 转录因子的抑制，存在于慢肌祖细胞中。在这里，我们鉴定了 sox6 的顺式调控序列，这些序列以依赖于 Prdm1a 的方式驱动快肌特异性表达。我们表明，sox6 的转录随后在慢肌纤维中被去抑制，而 Sox6 蛋白仍然局限于快肌纤维中。我们发现，sox6 的翻译抑制是由 miR-499 介导的，miR-499 的慢肌特异性表达又受到 Prdm1a 的控制，形成一个调节环，启动并维持慢肌谱系。
