Mechanism of transcription and coupling to protein homeostasis in embryonic stem cells

胚胎干细胞转录及蛋白稳态耦合机制

• 批准号: 151656211
• 负责人: Professor Dr. Michael Meisterernst
• 金额: --
• 依托单位: Stem Cell Research Laboratory
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/151656211?language=en
• 关键词: Mechanism; transcription; coupling; protein; homeostasis

The observation that many distinct somatic cells can be reprogrammed into ES cells raises interesting questions about the specifics of a hypothetical ground-state program governing them. In fact, ESCs specifically transcribe a defined group of pluripotency gene and they also allow efficient transcription of house keeping genes. In parallel ESCs repress a large number of differentiation genes using both pluripotency regulators and polycomb proteins. The pluripotent cells are unique as they have a particular accessible chromatin structure and express high concentrations of both general transcription factors and gene specific repressors. Although regulatory principles related to pluripotency have been illuminated at least in part in ESCs, very little is known about the contribution of the basal transcription machine. Here will generally ask whether RNA polymerase II transcription in ES cells follows specific distinct rules. One experimental line aims at comparing genes that are either downregulated during differentiation (like the Oct4 gene) or remain on (house keeping gene) both in vitro and in vivo. To facilitate an unbiased view on the protein functions we will develop and utilize functional in vitro transcription systems based on ES cell extracts. In a joint program with Ying Jin we will extend our investigations to the influence of protein degradation on transcription with a focus on the E3 ligase wwp2.

许多不同的体细胞可以被重新编程为ES细胞，这一观察结果引发了一个有趣的问题，即一个假设的基态程序控制它们的细节。事实上，ESC特异性地转录一组确定的多能性基因，并且它们还允许管家基因的有效转录。同时，ESC使用多能性调节剂和polycomb蛋白抑制大量分化基因。多能细胞是独特的，因为它们具有特定的可接近的染色质结构，并表达高浓度的通用转录因子和基因特异性阻遏物。虽然调控原则有关的多能性已阐明至少部分在胚胎干细胞，很少有人知道的基础转录机器的贡献。这里一般会问RNA聚合酶II在ES细胞中的转录是否遵循特定的独特规则。一个实验系旨在比较在体外和体内分化期间下调的基因（如Oct4基因）或保持不变的基因（管家基因）。为了促进对蛋白质功能的公正看法，我们将开发和利用基于ES细胞提取物的功能性体外转录系统。在与Ying Jin的一个联合项目中，我们将把我们的研究扩展到蛋白质降解对转录的影响，重点是E3连接酶wwp2。