Research Profile

Cellular differentiation is driven by specialized transcription factors that elicit changes in gene expression by binding to regulatory regions in DNA and activating hundreds of cell-type-specific genes. DNA is wrapped around histone proteins decorated with various epigenetic modifications that modulate the compaction of the whole chromatin and regulate access of transcription factors to the genetic material. How interactions between the transcription factors, cofactors, and chromatin result in precise and robust control over the vastly complex genome are central questions in cell biology and development. High-resolution microscopy revealed that the proteins needed to activate transcription, such as the Mediator and RNA Pol-II complexes, form dense assemblies or condensates at the sites of gene activation during differentiation. The reorganization of transcriptional components into various nuclear bodies is also a hallmark of a stress response. Our lab aims to dissect the mechanisms that lead to the formation of nuclear condensates, determine their molecular composition, and understand their functional relevance. We study the spatial organization of transcription in embryonic development and stress response using a cross-disciplinary approach that relies on biochemical reconstitution and functional studies in a nematode Caenorhabditis elegans. Since the fundamental mechanisms that govern the spatial regulation of transcription are likely conserved, we hope that our work paves the way for new therapeutic strategies against diseases caused by imbalanced gene regulation.

Current research activities

• biochemical reconstitution of transcriptional condensates
• microscopic characterization and functional studies of nuclear condensates during cell-fate determination and stress response
• identification of novel regulators of cell fate determination and stress response in C. elegans embryos using genetic screens

Selected Publications

Morin, J. A.*, Wittmann, S.*, Choubey, S.*, Klosin, A., Golfier, S., Hyman, A. A., Julicher, F., Grill, S. W. (2022). Sequence-dependent surface condensation of a pioneer transcription factor on DNA. Nature Physics, 18(3), 271-276. (*equal contribution) https://doi.org/10.1038/s41567-021-01462-2

Klosin, A.*, Oltsch, F.*, Harmon, T., Honigmann, A., Julicher, F., Hyman, A. A., & Zechner, C. (2020). Phase separation provides a mechanism to reduce noise in cells. Science, 367(6476), 464-468. (*equal contribution) https://doi.org/10.1126/science.aav6691

Klosin, A., & Hyman, A. A. (2017). Molecular biology: A liquid reservoir for silent chromatin. Nature, 547(7662), 168-170. https://doi.org/10.1038/nature23089

Klosin, A.*, Reis, K.*, Hidalgo-Carcedo, C., Casas, E., Vavouri, T., & Lehner, B. (2017). Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory. Science Advances, 3(8), e1701143. (*equal contribution) https://doi.org/10.1126/sciadv.1701143

Klosin, A., Casas, E., Hidalgo-Carcedo, C., Vavouri, T., & Lehner, B. (2017). Transgenerational transmission of environmental information in C. elegans. Science, 356(6335), 320-323. https://doi.org/10.1126/science.aah6412

Klosin, A., & Lehner, B. (2016). Mechanisms, timescales and principles of trans-generational epigenetic inheritance in animals. Curr Opin Genet Dev, 36, 41-49. https://doi.org/10.1016/j.gde.2016.04.001