Host: Liang Tong
Title: Mechanisms of chromatin transcription
Abstract: Our laboratory combines integrated structural biology with functional genomics and computational biology to study the mechanisms of gene transcription and its regulation in a chromatin context. In a long-term effort, we arrived at mechanistic insights into transcription initiation at promoters of protein-coding genes (Plaschka et al. Nature 2015, 2016; Nozawa et al. Nature 2017; Schilbach et al. Nature 2017). We also reported the molecular basis for understanding transcription regulation at the step of elongation of the mRNA chain in the promoter-proximal region (Vos and Farnung Nature 2018; Vos et al. Nature 2018). These processes depend on multiple phosphorylation events, and such phosphorylation may control the partitioning of RNA polymerase II between different nuclear condensates (Boehning et al., NSMB 2018). To complement the structural studies, we also developed transient transcriptome sequencing (TT-seq), which monitors RNA synthesis and regulatory enhancer landscapes at high temporal resolution(Schwalb Science 2016; Demel Mol. Syst. Biol. 2017). In recent work, we have combined functional genomics and kinetic modeling to derive kinetic insights into transcriptonal regulation genome-wide (Gressel, Schwalb et al. Leonhardt, Eick, and Cramer, eLife 2017). In my presentation I will concentrate on the most recent findings and unpublished data on transcription regulation in a chromatin context. I will provide insights into the mechanisms of how a pioneer transcription factor, Sox2, invades the nucleosome (Dodonova et al., unpublished), how a chromatin remodeling complex of the SWI/SNF family establishes a mature nucleosome-depleted region (Wagner et al., unpublished), and how Pol II may progress through nucleosomes (Farnung Nature 2017; Farnung Nature Comm. 2018).