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At IMB, we explore the molecular biology of the nucleus with an overarching focus on gene regulation, epigenetics & genome stability

The role of protein disorder in transcriptional regulation

Sina Wittmann

Transcription is one of the most fundamental processes of life. Precise transcriptional regulation in time and space is needed for proper development and to adequately react to environmental changes. Transcriptional activation is regulated by a complex, multi-step process that starts with the recognition of DNA elements through gene-specific transcription factors. These factors subsequently recruit downstream factors including RNA polymerase II, so that RNA synthesis can begin. Recently, it was discovered that transcription initiation sites contain protein condensates with liquid-like properties. This exciting new finding has attracted much attention, as it can potentially explain cellular observations that were previously puzzling. This includes the simultaneous firing of different genes or the bursting behaviour of transcription. While we recently succeeded in reconstituting the formation of transcription factor condensates in vitro, little is known about their function and regulation inside cells. We in the Wittmann lab try to decipher how condensates work to precisely regulate transcription so that different tissues can develop.

Research website

Positions held

  • Since 2023: Group Leader, Institute of Molecular Biology (IMB),Mainz, Germany
  • 2017 – 2022: Postdoctoral researcher, Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden

Education

  • 2017: PhD in Biochemistry, University of Oxford
  • 2012: MSc in Biochemistry, University of Regensburg
  • 2009: BSc in Biochemistry, University of Regensburg

Selected publications by Sina Wittmann

Morin# JA, Wittmann# S, Choubey# S, Klosin A, Golfier S, Hyman AA, Jülicher F, Grill SW (2022) Sequence-dependent surface condensation of a pioneer transcription factor on DNA. Nat. Phys. 18, 271–276 Link

Krainer G, Welsh TJ, Joseph JA, Espinosa JR, Wittmann S, de Csilléry E, Sridhar A, Toprakcioglu Z, Gudiškytė G, Czekalska MA, Arter WE, Guillén-Boixet J, Franzmann TM, Qamar S, George-Hyslop PS, Hyman AA, Collepardo-Guevara R, Alberti S, Knowles TPJ (2021) Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions. Nat. Commun. 12, 1085 Link

Guillén-Boixet J, Kopach A, Holehouse AS, Wittmann S, Jahnel M, Schlüßler R, Kim K, Trussina IREA, Wang J, Mateju D, Poser I, Maharana S, Ruer-Gruß M, Richter D, Zhang X, Chang YT, Guck J, Honigmann A, Mahamid J, Hyman AA, Pappu RV, Alberti S, Franzmann TM, (2020) RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation. Cell. 181, 346-361.e17 Link

Wittmann S, Alberti S (2019) ERα condensates: chronic stimulation is hard to ignore. Nat. Struct. Mol. Biol. 26, 153–154 Link

Wittmann S, Renner M, Watts BRBR, Adams O, Huseyin M, Baejen C, El Omari K, Kilchert C, Heo DH DH, Kecman T, Cramer P, Grimes JMJM, Vasiljeva L (2017) The conserved protein Seb1 drives transcription termination by binding RNA polymerase II and nascent RNA. Nat. Commun. 8, 14861 Link