Poepsel Lab

Structure and Biochemistry of Epigenetic Regulators

We want to understand molecular links between chemical protein modifications and gene regulation. We are studying the enzymes that introduce or remove modifications, and effector proteins that recognize them. Using cryo-electron microscopy (cryo-EM), we visualize how their 3D structure and dynamics enable them to be active at the right time and in the right place within the genome. This knowledge may help to understand how epigenetic changes contribute to diseases such as cancer. 

Selected Publications

  • Kasinath V, Beck C, Sauer P, Poepsel S, Kosmatka J, Faini M, Toso D, Aebersold R, Nogales E. 2021. JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science. Jan 22;371(6527):eabc3393. doi: 10.1126/science.abc3393.
  • Finogenova K, Bonnet J, Poepsel S, Schäfer IB, Finkl K, Schmid K, Litz C, Strauss M, Benda C, Müller J. 2020. Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. Elife. 2020 Nov 19;9:e61964. doi: 10.7554/eLife.61964.
  • Kasinath, V*, Poepsel, S*, and Nogales, E. 2019. Recent Structural Insights into Polycomb Repressive Complex 2 Regulation and Substrate Binding (REVIEW)Biochemistry. 58(5):346-354. 
  • Poepsel, S, Kasinath, V and Nogales, E. 2018. Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. Nature Structural & Molecular Biology. 25, 154-162. 
  • Kasinath, V., Faini, M., Poepsel, S., Reif, D., Feng X.A., Stjepanovic, G., Aebersold, R. and Nogales, E. 2018. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science. 359: 940-944. 
  • Kellogg, E.H., Hejab, N., Poepsel, S., Downing, K.H., DiMaio, F., Nogales, E. 2018. Near-atomic model of microtubule-tau interactions. Science. 360(6394):1242-1246. 
  • Poepsel, S., Sprengel, A., Sacca, B., Kaschani, F., Kaiser, M., Gatsogiannis, C., Raunser, S., Clausen, T., Ehrmann, M.: Determinants of amyloid fibril degradation by the PDZ protease HTRA1. Nature Chemial Biology. 11: 862-9. 
  • *Tennstaedt, A., *Popsel, S., Truebestein, L., et al. 2012. Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates. Journal of Biological Chemistry 287: 20931-20941.
  • *Merdanovic, M., *Mamant, N., *Meltzer, M., *Poepsel, S., Auckenthaler, A., Melgaard, R., et al. 2010. Determinants of structural and functional plasticity of a widely conserved protease chaperone complex. Nature Structural & Molecular Biology. 17: 837-843.