GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis
GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis
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DOI：
10.1111/j.1365-2443.2005.00873.x
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发表时间：
2005-07-01
期刊：
影响因子：
2.1
通讯作者：
Handa, H
中科院分区：
文献类型：
--
作者：
Deléhouzée, S;Yoshikawa, T;Handa, H
肌细胞分化或肌生成是一个特征明确的过程，涉及特定基因组有序表达。肌生成的先决条件是退出细胞周期，这与肿瘤抑制因子Rb的上调有关。在这项研究中，我们设置为调查的Rb启动子，允许适当的上调分化成肌细胞的调节机制。我们报告Rb的表达受转录因子GABP，HCF-1和YY 1的调节。在诱导分化之前，Rb以低水平表达，并且GABP和YY 1都存在于启动子上。YY 1，这对Rb的表达发挥抑制作用，从启动子中删除的细胞通过肌生成和易位从细胞核到细胞质。另一方面，在诱导分化时，GABP辅因子HCF-1被募集到启动子并与GABP共激活启动子。RNAi介导的HCF-1敲低导致Rb上调以及肌管形成的抑制。这些结果表明，Rb启动子是受调节的积极和消极的因素，这种复杂的激活机制是至关重要的，让准确的Rb基因上调观察肌发生过程中。
Muscle cell differentiation, or myogenesis, is a well-characterized process and involves the expression of specific sets of genes in an orderly manner. A prerequisite for myogenesis is the exit from the cell cycle, which is associated with the up-regulation of the tumor suppressor Rb. In this study, we set to investigate the regulatory mechanism of the Rb promoter that allows adequate up-regulation in differentiating myoblasts. We report that Rb expression is regulated by the transcription factors GABP, HCF-1 and YY1. Before induction of differentiation, Rb is expressed at a low level and GABP and YY1 are both present on the promoter. YY1, which exerts an inhibitory effect on Rb expression, is removed from the promoter as cells advance through myogenesis and translocates from the nucleus to the cytoplasm. On the other hand, upon induction of differentiation, the GABP cofactor HCF-1 is recruited to and coactivates the promoter with GABP. RNAi-mediated knock-down of HCF-1 results in inhibition of Rb up-regulation as well as myotube formation. These results indicate that the Rb promoter is subject to regulation by positive and negative factors and that this intricate activation mechanism is critical to allow the accurate Rb gene up-regulation observed during myogenesis.