Molekulare Mechanismen und physiologische Funktion der Transcriptionscofactors PC4

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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.