Molekulare Mechanismen und physiologische Funktion der Transcriptionscofactors PC4

要了解决定生长和分化的细胞程序，需要对基因控制的机制有详细的了解。在真核生物中，辅因子介导调节因子的作用并控制基础RNA聚合酶II机器的活性。这里的焦点将放在PC4上，它是第一个在哺乳动物中克隆的通用辅因子。PC4是一种DNA结合蛋白，通过RNA聚合酶II的活性对转录产生积极和消极的影响。它的DNA结合特性也使其在原则上有资格在其他过程中发挥作用，如DNA修复。我们关于PC4功能的大部分知识都是基于体外分析的。PC4在哺乳动物中的生理功能尚不清楚。在这里，我们建议使用细胞和小鼠模型来研究它的生物学作用和潜在的分子机制。目的是了解PC4与基因组的相互作用，它对涉及基因控制和DNA完整性的核机器的影响，以及它在发育中的生物体中的作用。

Understanding cellular programs that determine growth and differentiation requires detailed insight into the mechanisms of gene control. Cofactors mediate the action of regulatory factors and control the activity of the basal RNA polymerase II machine in eukaryotes. Here the focus will be on PC4, which is the first general cofactor to be cloned in mammals. PC4 is a DNA binding protein that affects transcription by RNA polymerase II activity both positively and negatively. Its DNA-binding properties also qualify it in principle to act in other processes, such as DNA repair. Much of our knowledge about PC4 function is based on in vitro analyses. The physiological functions of PC4 in mammals remain unclear. Here we propose to study its biological roles and the underlying molecular mechanisms using cellular and mouse models. The goal is to understand the interactions of PC4 with the genome, its effects on the nuclear machines involved in gene control and DNA integrity and its role in a developing organism.