Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells

Jeffrey C. Wyzykowski; Therry I. Winata; Natalia Mitin; Elizabeth J. Taparowsky; Stephen F. Konieczny

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Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells

机译：在增生的成肌干细胞中新型MyoD基因靶标的鉴定

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A major control point for skeletal myogenesis revolves around the muscle basic helix-loop-helix gene family that includes MyoD, Myf-5, myogenin, and MRF4. Myogenin and MRF4 are thought to be essential to terminal differentiation events, whereas MyoD and Myf-5 are critical to establishing the myogenic cell lineage and producing committed, undifferentiated myogenic stem cells (myoblasts). Although mouse genetic studies have revealed the importance of MyoD and Myf-5 for myoblast development, the genetic targets of MyoD and Myf-5 activity in undifferentiated myoblasts remain unknown. In this study, we investigated the function of MyoD as a transcriptional activator in undifferentiated myoblasts. By using conditional expression of MyoD, in conjunction with suppression subtractive hybridizations, we show that the Id3 and NP1 (neuronal pentraxin 1) genes become transcriptionally active following MyoD induction in undifferentiated myoblasts. Activation of Id3 and NP1 represents a stable, heritable event that does not rely on continued MyoD activity and is not subject to negative regulation by an activated H-Ras G12V protein. These results are the first to demonstrate that MyoD functions as a transcriptional activator in myogenic stem cells and that this key myogenic regulatory factor exhibits different gene target specificities, depending upon the cellular environment.

机译：骨骼肌发生的主要控制点围绕着肌肉基本的螺旋-环-螺旋基因家族，包括 MyoD ， Myf-5 ， myogenin ，和 MRF4 。肌生成素和MRF4被认为是终末分化事件必不可少的，而MyoD和Myf-5对于建立成肌细胞谱系并产生定型，未分化的成肌干细胞（成肌细胞）至关重要。尽管小鼠遗传学研究表明MyoD和Myf-5对于成肌细胞的重要性，但未分化成肌细胞中MyoD和Myf-5活性的遗传靶标仍然未知。在这项研究中，我们调查了MyoD作为未分化成肌细胞中转录激活因子的功能。通过使用条件表达的MyoD，与抑制性消减杂交相结合，我们显示 Id3 和 NP1 （神经性五肽毒素1）基因在未分化的成肌细胞中受到MyoD诱导后具有转录活性。 Id3 和 NP1 的激活表示一个稳定的，可遗传的事件，它不依赖于持续的MyoD活性，也不受激活的H-Ras G12V蛋白的负调控。这些结果首次证明MyoD在成肌干细胞中起转录激活剂的作用，并且取决于细胞环境，该关键的成肌调节因子表现出不同的基因靶标特异性。 展开▼

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《Molecular and Cellular Biology》 |2002年第17期|共10页

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Jeffrey C. Wyzykowski; Therry I. Winata; Natalia Mitin; Elizabeth J. Taparowsky; Stephen F. Konieczny;
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中图分类细胞生物学;

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2. Loss of MyoD and Myf5 in Skeletal Muscle Stem Cells Results in Altered Myogenic Programming and Failed Regeneration [J] . Masakazu Yamamoto, Nicholas P. Legendre, Arpita A. Biswas, Stem Cell Reports . 2018,第3期

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3. MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury [J] . Ju Ang Kim, Yun Hee Shon, Jeong Ok Lim, Stem Cell Research & Therapy . 2013,第6期

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6. Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells [O] . Jeffrey C. Wyzykowski, Therry I. Winata, Natalia Mitin, 2002

机译：在增生的成肌干细胞中新型MyoD基因靶标的鉴定

7. Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells [O] . Wyzykowski, Jeffrey C., Winata, Therry I., Mitin, Natalia, 2002

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Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells

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