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

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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.