In plants, animals, and humans at the very first early stages of embryo development the genome is transcriptionally inactive. Only after several cell division cycles genome gets activated and takes over the control over the development. Together with our experimental collaborators (group of Nadine Vastenhouw, MPI-CBG Dresden) we could show that the silencing of the transcription is achieved via histone proteins competing with transcription activation factors. The chromatin bound to histones and forming nucleosomes is inaccessible for transcription factors. As DNA keeps replicating, the histones get depleted and eventually loose the competition, allowing for the onset of transcription. We now exploit the onset of genome activation to investigate the effect of transcriptional activity on the chromatin structure. This project involves a series of innovative biological techniques and proposes a novel concept of phase separation in the nucleus which is driven by the RNA polymerase activity (see figure for illustration of the model). Actively transcribing chromatin (red) creates an interface of the inactive chromatin (black) with the RNA and RNA-binding proteins (blue), where the polymerase enzyme might be viewed as an active surfactant.
In the future we will develop theoretical basis of such phase-separating system and check the predictions of the model by perturbing the transcription levels in developing embryos.
Transcription organizes euchromatin similar to an active microemulsion; L. Hilbert, Y. Sato, H. Kimura, F. Jülicher, A. Honigmann, V. Zaburdaev, N. Vastenhouw, bioRxiv (2018)
A tunable refractive index matching medium for live imaging cells, tissues and model organisms; T. Boothe, L. Hilbert, M. Heide, L. Berninger, W. B. Huttner, V. Zaburdaev, N. L. Vastenhouw, E. W. Myers, D. N. Drechsel, and J. C. Rink, eLife 2017; 6: e27240 (2017)
Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos; S. R. Joseph, M. Pálfy, L. Hilbert, M. Kumar, J. Karschau, V. Zaburdaev, A. Shevchenko, N. L. Vastenhouw, eLife 2017;6:e23326 (2017)