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Determinants of Myogenic Specificity within MyoD Are Required for Noncanonical E Box Binding

机译：非经典E盒结合需要MyoD中的肌原性特异性的决定因素

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The MyoD family of basic helix-loop-helix (bHLH) transcription factors has the remarkable ability to induce myogenesis in vitro and in vivo. This myogenic specificity has been mapped to two amino acids in the basic domain, an alanine and threonine, referred to as the myogenic code. These essential determinants of myogenic specificity are conserved in all MyoD family members from worms to humans, yet their function in myogenesis is unclear. Induction of the muscle transcriptional program requires that MyoD be able to locate and stably bind to sequences present in the promoter regions of critical muscle genes. Recent studies have shown that MyoD binds to noncanonical E boxes in the myogenin gene, a critical locus required for myogenesis, through interactions with resident heterodimers of the HOX-TALE transcription factors Pbx1A and Meis1. In the present study, we show that the myogenic code is required for MyoD to bind to noncanonical E boxes in the myogenin promoter and for the formation of a tetrameric complex with Pbx/Meis. We also show that these essential determinants of myogenesis are sufficient to confer noncanonical E box binding to the E12 basic domain. Thus, these data show that noncanonical E box binding correlates with myogenic potential, and we speculate that the myogenic code residues in MyoD function as myogenic determinants via their role in noncanonical E box binding and recognition.
机译：碱性螺旋-环-螺旋（bHLH）转录因子的MyoD家族具有在体内和体外诱导肌发生的显着能力。这种成肌特异性已被映射到基本域中的两个氨基酸，丙氨酸和苏氨酸，称为成肌密码。从蠕虫到人类，所有MyoD家族成员都保留了肌原性特异性的这些基本决定因素，但它们在肌发生中的功能尚不清楚。肌肉转录程序的诱导要求MyoD能够定位并稳定结合关键肌肉基因启动子区域中存在的序列。最近的研究表明，MyoD通过与HOX-TALE转录因子Pbx1A和Meis1的常驻异二聚体相互作用，与 myogenin 基因中的非规范E盒结合，这是肌肉生成所必需的关键基因座。在本研究中，我们表明MyoD绑定到 myogenin 启动子中的非规范E框以及与Pbx / Meis形成四聚体复合物所需的肌原性密码。我们还显示，肌发生的这些基本决定因素足以赋予非规范E框绑定到E12基本域。因此，这些数据表明，非经典的E盒结合与成肌潜能相关，我们推测MyoD中的成肌代码残基通过它们在非经典的E盒结合和识别中的作用而作为成肌决定簇。

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