Cell Nucleus Structures; Chromosomal Position Effects; Histone Code; Mediator Complex; Nuclear Pore Complex Proteins; RNA Polymerase II; Tardigrada; Ubiquitin-Protein Ligase Complexes
Nuclear Pores - Regulators of Chromatin and Membrane Dynamics
Nuclear pore complexes (NPCs) function as gates that control the transport of cargo across the nuclear membrane. Beyond that NPCs interact with chromatin and influence the decoding of genetic information. We recently discovered that dedicated adaptors such as TREX-2 and Mediator regulate transcription by RNA Polymerase II. These investigations are related to our general interest in how genes are turned on and off, for example by chromatin ubiquitination. We also revealed a new function of the NPC in remodelling the nuclear membrane to promote NPC production and nuclear envelope integrity underscoring the notion that NPCs fulfill unconventional duties beyond transport. Recently, we started a new line of research with the aim of Decrypting Cryptobiosis in Tardigrades: Tardigrades (water bears) are one of the most resilient and fascinating animals known: they withstand conditions that would be fatal to nearly all other life forms on earth. They survive this by falling into an enigmatic state called cryptobiosis, in which they are neither dead nor alive. We are studying selected aspects of Tardigrade biology aiming to unravel the molecular secrets behind their outstanding robustness, specifically, how nuclear architecture and function is preserved under extremes.
Techniques, methods & infrastructure
We use biochemical, structural, genome-wide and cell biological methods to address these questions. Functional reconstitution is central to our approach, as the ability to reconstruct systems from scratch offers key insights into what is minimally needed and how mechanisms emerge from component parts.
- Gallego, L.D. et al., 2016. Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6-Bre1. Proceedings of the National Academy of Sciences, 113(38), pp.10553-10558. Available at: http://dx.doi.org/10.1073/pnas.1606863113.
- Schneider, M. et al., 2015. The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell, 162(5), pp.1016-1028. Available at: http://dx.doi.org/10.1016/j.cell.2015.07.059.
- Turco, E. et al., 2014. Monoubiquitination of Histone H2B Is Intrinsic to the Bre1 RING Domain-Rad6 Interaction and Augmented by a Second Rad6-binding Site on Bre1. Journal of Biological Chemistry, 290(9), pp.5298-5310. Available at: http://dx.doi.org/10.1074/jbc.M114.626788.
- Meszaros, N. et al., 2015. Nuclear Pore Basket Proteins Are Tethered to the Nuclear Envelope and Can Regulate Membrane Curvature. Developmental Cell, 33(3), pp.285-298. Available at: http://dx.doi.org/10.1016/j.devcel.2015.02.017.
- Köhler, A. et al., 2010. Structural Basis for Assembly and Activation of the Heterotetrameric SAGA Histone H2B Deubiquitinase Module. Cell, 141(4), pp.606-617. Available at: http://dx.doi.org/10.1016/j.cell.2010.04.026.