Transcription regulation in time and space: Engineered cell systems to modulate the epigenetic chromatin structure: The role of Methyl-CpG-binding protein 2

Transcription processing and chromatin structural changes are intertwined processes in the nucleus. In this thesis we focused on the dynamic interplay of chromatin and its widespread functions such as genome stability and transcription regulation. We studied the effect of targeting the epigenetic regulatory protein Methyl CpG binding protein2 (MeCP2) and measure alterations in chromatin structure and transcription regulation in real-time, in order to unravel the causal relationship between the epigenetic chromatin state and transcriptional repression in time and space.
In this thesis we focus on MeCP2, an epigenetic regulatory protein well known from MeCP2 related diseases caused by mutations in the MeCP2 coding region. We discuss the various different functionalities of MeCP2, i.e. to act as an activator as well as a repressor. Moreover, we conclude that determining molecular functioning of MeCP2 is essential to find ways to monitor or treat MeCP2 related disease development. In our reporter gene array studies we show that MeCP2 is able to alter chromatin structure and timing of transcription repression. These data suggest that MeCP2 acts as a 'facilitator' protein being able to either induce gene activity or silencing based on the facilitated sequence of events. This facilitator functioning might be a general concept of the concerted action of epigenetic regulatory proteins to establish and maintain transcription patterns.