Regulation of Rb gene expression by an MBD2-interacting zinc finger protein MIZF during myogenic differentiation.

Regulation of Rb gene expression by an MBD2-interacting zinc finger protein MIZF during myogenic differentiation.
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DOI:
10.1016/j.bbrc.2004.10.090
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发表时间:
2004-12
影响因子:
3.1
通讯作者:
M. Sekimata;Y. Homma
M. Sekimata;Y. Homma
中科院分区:
生物学4区
文献类型:
--
作者:
M. Sekimata;Y. Homma

文献摘要

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Rb基因表达的诱导是肌源性分化过程中的关键事件。我们最近证明,Rb基因的转录被MIZF抑制,MIZF以前被描述为MBD 2结合伴侣。在这里,我们展示了MIZF作为肌源性分化调节剂的新作用。在未分化的C2 C12成肌细胞中检测到MIZF mRNA,但其表达在成肌过程中下降,与Rb mRNA的增加相关。为了检测MIZF在调节肌源性分化中的功能,我们用腺病毒载体转导C2 C12成肌细胞以组成性地产生高水平的MIZF。当切换到分化培养基中时,这些细胞显示Rb以及分化标记物如肌生成素和肌钙蛋白-T的表达降低,因此不能分化成多核肌管。这些结果表明,转录抑制Rb的MIZF可能是肌细胞分化的关键决定因素之一。
The induction of Rb gene expression is a key event in the process of myogenic differentiation. We recently demonstrated that transcription of the Rb gene is repressed by MIZF, previously characterized as an MBD2-binding partner. Here we show the new roles of MIZF as a regulator of myogenic differentiation. MIZF mRNA was detected in undifferentiated C2C12 myoblasts but its expression decreased during myogenesis, correlating with an increase in Rb mRNA. To examine the function of MIZF in regulating myogenic differentiation, we transduced C2C12 myoblasts with adenoviral vectors to constitutively produce MIZF at high levels. When switched to differentiation medium, these cells showed decreased expression of Rb as well as differentiation markers such as myogenin and Troponin-T, and consequently could not differentiate into multinucleated myotubes. These results suggest that transcriptional repression of Rb by MIZF could be one of the critical determinants in myogenic differentiation.