Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1793, Issue 7, Pages 1144-1155Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2009.01.019
Keywords
ZBP-89; Myogenesis; C2C12; p21; MyoD; Mrf4; Myogenin
Categories
Funding
- NHLBI
- National Institutes of Health (NIH) [HL-45422]
- American Heart Mid-Atlantic [0415464U]
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Myogenesis involves the complex interplay between the down-regulation of non-muscle genes and the upregulation 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 Kruppel-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 realtime 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 overexpression 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. (C) 2009 Elsevier B.V. All rights reserved.
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