Over-expression of the transcription factor, ZBP-89, leads to enhancement of the C2C12 myogenic program.
Over-expression of the transcription factor, ZBP-89, leads to enhancement of the C2C12 myogenic program.
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DOI：
10.1016/j.bbamcr.2009.01.019
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Zehner ZE
中科院分区：
文献类型：
--
作者：
Salmon M;Owens GK;Zehner ZE
Myogenesis involves the complex interplay between the down-regulation of non-muscle genes and the up-regulation of muscle-specific genes. This interplay is controlled by the myogenic regulatory factors Myf5, MRF4, MyoD and myogenin. To trigger the up-regulation of these muscle-specific factors, certain environmental cues, such as the removal of serum, signal C2C12 myoblast cells to withdraw from cell cycle, fuse and activate muscle-specific genes. Here, the level of ZBP-89 (zfp148), a Krüppel-like transcription factor, has been shown to increase during myogenesis. Over-expression of ZBP-89, via adenoviral infection, led to the enhancement of the myogenic program without requiring the removal of serum. Quantitative real-time PCR and ChIP assays documented that ZBP-89 promoted the down-regulation of Pax7 coupled with the up-regulation of MRF4 and MyoD to regulate C2C12 differentiation in vitro. In addition, ZBP-89 over-expression up-regulated p21 and Rb while promoting the down-regulation of cyclinA and cyclinD1. In converse, the diminution of ZBP-89 by siRNA promoted the retention of myogenic and cell cycle regulators at myoblast levels resulting in a concomitant delay of the myogenic program. From these studies we conclude that the transcription factor ZBP-89 plays an important role in the timing of the myogenic program.
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