DISPLACEMENT OF BRDURD-INDUCED YY1 BY SERUM RESPONSE FACTOR ACTIVATES SKELETAL ALPHA-ACTIN TRANSCRIPTION IN EMBRYONIC MYOBLASTS
DISPLACEMENT OF BRDURD-INDUCED YY1 BY SERUM RESPONSE FACTOR ACTIVATES SKELETAL ALPHA-ACTIN TRANSCRIPTION IN EMBRYONIC MYOBLASTS
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DOI：
10.1073/pnas.89.20.9814
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
SCHWARTZ, RJ
中科院分区：
文献类型：
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作者：
LEE, TC;SHI, Y;SCHWARTZ, RJ
骨骼肌α-肌动蛋白基因的肌肉限制性转录部分由正调节因子血清反应因子（SRF）和负调节因子F-ACT 1控制，后者竞争性结合最近端血清反应元件（SRE 1）。我们在这里表明，F-ACT 1是相同的转录因子最近克隆和描述为YY 1，NF-E1，δ，或UCRBP。我们发现，虽然SRF的DNA结合活性在肌发生过程中积累，YY 1的同时减少。BrdUrd处理不能分化的成肌细胞表现出最高水平的YY 1和最低水平的SRF活性。转染SRF可以克服BrdUrd诱导的YY 1的抑制作用，直接反式激活骨骼α-肌动蛋白启动子。反式激活依赖于完整的SRE DNA元件，并需要SRF的DNA结合/二聚化结构域以及其C-末端富含丝氨酸和苏氨酸的一半。由于YY 1和SRF的功能似乎是发育调节的，它们的结合位点在SRE上的收敛构成了一个综合机制，从而可以完成时间和空间肌肉基因表达。
Muscle-restricted transcription of the skeletal alpha-actin gene is controlled in part by a positive regulator, serum response factor (SRF), and a negative regulator, F-ACT1, which bind competitively to the most proximal serum response element (SRE1). We show here that F-ACT1 is identical to a transcription factor recently cloned and described as YY1, NF-E1, delta, or UCRBP. We found that although the DNA-binding activity of SRF accumulates during myogenesis, that of YY1 diminishes simultaneously. Myoblasts rendered incapable of differentiation by BrdUrd treatment exhibited the highest level of YY1 and the lowest level of SRF activities. Transfected SRF could directly transactivate the skeletal alpha-actin promoter by overcoming the inhibitory effect of BrdUrd-induced YY1. The transactivation depends on intact SRE DNA elements and requires the DNA-binding/dimerization domain of SRF as well as its C-terminal half rich in serines and threonines. Since the functions of YY1 and SRF appear to be developmentally regulated, the convergence of their binding sites upon the SRE constitutes an integrated mechanism whereby temporal and spatial muscle gene expression may be accomplished.