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首页> 外文期刊>Biology Open >Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer
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Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer

机译：通过与Myf5肢体增强剂相互作用的同源盒蛋白来微调肌发生的开始

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Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120?kb upstream of the Mrf4-Myf5 locus. An enhancer, located at ?57/?58?kb from Myf5 , is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles. Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element. Myogenic progenitor cells that will form the future muscle masses of the limbs express the factors necessary for Myf5 activation when they delaminate from the hypaxial dermomyotome and migrate into the forelimb bud, however they do not activate Myf5 and the myogenic programme until they have populated the prospective muscle masses. We show that Msx1 and Meox2 homeodomain-containing transcription factors bind in vitro and in vivo to specific sites in the 145-bp element, and are implicated in fine-tuning activation of Myf5 in the forelimb. Msx1, when bound between Pax and Six sites, prevents the binding of these key activators, thus inhibiting transcription of Myf5 and consequent premature myogenic differentiation. Meox2 is required for Myf5 activation at the onset of myogenesis via direct binding to other homeodomain sites in this sequence. Thus, these homeodomain factors, acting in addition to Pax3 and Six1/4, fine-tune the entry of progenitor cells into myogenesis at early stages of forelimb development.
机译：脊椎动物的骨骼肌发生是在发育过程中，通过激活肌原性调节基因的特定控制元件，在骨骼肌形成的不同部位开始的。在小鼠胚胎中，Myf5是第一个表达的成肌测定基因，其时空调控需要多个增强子序列，在Mrf4-Myf5基因座上游延伸超过120kb。位于Myf5的？57 /？58？kb处的增强子负责其在源于somite轴突域的成肌细胞中的激活，该细胞将形成肢体肌肉。 Pax3和Six1 / 4转录因子是该增强子的必需激活剂，作用于145-bp核心元件上。形成肢体未来肌肉群的成肌祖细胞在从近轴皮肌瘤脱层并移入前肢芽时表达Myf5激活所必需的因子，但是它们直到激活了前者后才激活Myf5和成肌程序。肌肉肿块。我们显示，Msx1和Meox2含Homeodomain的转录因子在体外和体内与145-bp元素中的特定位点结合，并牵涉前肢Myf5的微调激活。当在Pax和六个位点之间结合时，Msx1阻止了这些关键激活因子的结合，从而抑制了Myf5的转录并因此抑制了过早的成肌分化。通过直接结合到该序列中的其他同源域位点，在肌发生开始时，Myox5激活需要Meox2。因此，除了Pax3和Six1 / 4外，这些同源域因子还可以在前肢发育的早期阶段微调祖细胞进入肌发生的过程。

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