蛋白酶体限制了胚胎干细胞中的组织特异基因位点的容许转录
Henrietta Szutorisz1, Andrew Georgiou, László Tora
1Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK. henrietta.szutorisz@csc.mrc.ac.uk
Cell
|December 28, 2006
概括
蛋白酶体通过调节转录因子结合,防止胚胎干细胞中错误的基因激活. 抑制蛋白酶活性导致意外的基因表达,突出其在维持干细胞功能的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 干细胞分化依赖于精确的基因表达程序.
- 转录因子和RNA聚合酶II在调节区域调节基因激活.
研究的目的:
- 研究蛋白质酶在胚胎干细胞 (ES) 中调节基因转录中的作用.
- 确定蛋白酶活性如何影响转录因子和RNA聚合酶II与调控元素结合.
主要方法:
- 化学和siRNA介导的抑制蛋白酶体活动.
- 对转录因子和RNA聚合酶II结合特征的分析.
- 评估ES细胞中的蛋白质酶子单元结合和RNAi敲除后的情况.
主要成果:
- 蛋白质酶抑制增加了转录因子和RNA聚合酶II的结合.
- 抑制导致加密促进体的激活,表明转录异常.
- 有证据表明,26S蛋白质组在特定的调节元素上有针对性的组装.
结论:
- 蛋白酶体动态调节ES细胞基因域中的转录因子和Pol II循环.
- 蛋白质酶活性限制了允许的转录,保持基因处于增强状态.
- 这种调节对于防止干细胞早期发育过程中过早激活基因至关重要.
相关概念视频
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...


