Oral Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Towards the mechanisms of chromatin transcription (#56)

Patrick Cramer 1
  1. Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

Our laboratory combines structural biology with functional genomics and computational biology to study the mechanisms of gene transcription and its regulation in eukaryotic cells. Last year we could report the structure of the Pol II initiation complex (Plaschka Nature 2015, 2016; Nozawa Nature 2017; Schilbach Nature 2017). We also developed transient transcriptome sequencing (TT-seq), which can changes in RNA synthesis and enhancer landscapes at high temporal resolution (Schwalb Science 2016; Demel Mol. Syst. Biol. 2017). I will concentrate on our recent work and present the structures of paused and activated Pol II elongation complexes (Vos, Farnung et al., Nature 2018; Vos et al., Nature 2018) together with in vivo evidence for polymerase pausing during elongation controlling initiation (Gressel, Schwalb et al. Leonhardt, Eick, and Cramer, eLife 2017). The resulting molecular mechanism for Pol II activation supports a large body of work from many groups that was collected over the years on gene regulation. I will also discuss our recent work aimed at unraveling the intricate mechanisms of Pol II transcription through chromatin. In particular, I will discuss our structural studies of the chromatin remodeling enzyme Chd1 (Farnung Nature 2017) and present an unpublished structure of a transcribing Pol II-nucleosome complex that provides insights into how Pol II approaches a nucleosome for traversal. Finally, I will provide an outlook with respect to the next steps towards an understanding of the transcription of chromatin.