MyoD synergizes with the E-protein HEBβ to induce myogenic differentiation
MyoD synergizes with the E-protein HEBβ to induce myogenic differentiation
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DOI：
10.1128/mcb.02404-05
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Rudnicki, Michael A.
中科院分区：
文献类型：
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作者：
Parker, Maura H.;Perry, Robert L. S.;Rudnicki, Michael A.
碱性螺旋-环-螺旋转录因子的MyoD家族作为异二聚体与E-蛋白家族的成员一起起作用以诱导肌原性基因活化。E蛋白HEB被选择性剪接以产生α和β同种型。虽然这些分子的功能已经在其他细胞类型中进行了研究，但关于HEB蛋白在骨骼肌中的分子功能的问题仍然存在。我们的数据表明，HEB α表达在成肌细胞和肌管中保持不变，而HEB β在终末分化的早期阶段上调。在诱导分化后，MyoD-HEB β复合物结合肌细胞生成蛋白启动子的E1 E-盒，导致转录激活。重要的是，HEB β与MyoD的强制表达协同导致增殖成肌细胞中的早熟肌细胞生成素表达。然而，分化后，HEB α和HEB β与肌细胞生成素协同作用，而不是MyoD，以激活肌细胞生成素启动子。在成肌细胞中通过小干扰RNA特异性敲低HEB β阻断分化并抑制生肌蛋白转录的诱导。因此，HEB α和HEB β在通过肌源性分化协调肌源性因子活性的调节中发挥新的和中心的作用。
The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate alpha and beta isoforms. While the function of these molecules has been studied in other cell types, questions persist regarding the molecular functions of HEB proteins in skeletal muscle. Our data demonstrate that HEB alpha expression remains unchanged in both myoblasts and myotubes, whereas HEB beta is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEB beta complex bound the El E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEB beta with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEB alpha and HEB beta synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEB beta by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEB alpha and HEB beta play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation.