Lectures and seminars Centromeres and Interferon-Responsive Genes: Two Paradigms of Epigenetic Memory
Welcome to a seminar with Professor Lars Jansen from Oxford University!
About the talk
DNA is the classic substrate for inheritance. However, cells also possess mechanisms that maintain transient, yet heritable memory of past events alongside genetically encoded information. Chromatin plays a central role in maintaining such epigenetic memory through positive feedback mechanisms that replicate specialised chromatin domains during successive cell divisions. Our research aims to uncover how these mechanisms work.
One focus of the lab is the human centromere, defined by a unique, specialised chromatin structure essential for accurate chromosome segregation. Centromere identity is largely independent of the underlying DNA sequence and is instead specified by the histone H3 variant CENP-A. We discovered that CENP-A forms an exceptionally stable chromatin domain and is assembled through a cell cycle-coupled positive feedback mechanism that ensures faithful centromere propagation. We have recently developed methods to induce centromeres de novo that are inherited indefinitely, enabling us to discover how centromeres are established, regulated, and inherited with remarkable fidelity.
A second focus is a poorly understood phenomenon called “transcriptional memory”. We identified a unique class of genes that retain a mitotically heritable memory of prior interferon-gamma (IFNγ) exposure for weeks, even in rapidly proliferating cells. We recently discovered that this primed state is maintained in the complete absence of target gene expression and is independent of activating transcription factors. Instead, priming establishes a unique chromatin signature that is stably inherited through cell division and is functionally required for future hyperactivation.
We use these paradigms to provide new insight into how chromatin encodes and propagates epigenetic memory, with broad implications for chromosome inheritance, innate immunity, and cellular memory.
About the speaker
Lars Jansen is a native of the Netherlands. He received his PhD in Molecular Genetics in 2002 from Leiden University, where he studied nucleotide excision repair in budding yeast. He subsequently moved to San Diego, California, for postdoctoral training with Don Cleveland, focusing on mitosis and the discovery of epigenetic properties of human centromeres. From 2008 to 2018, he was a Principal Investigator at the Gulbenkian Institute near Lisbon, Portugal, where his work centered on the mechanisms of chromatin inheritance. Since 2018, his laboratory has been based in the Department of Biochemistry at the University of Oxford, where he is Professor of Molecular Genetics. He is also a Fellow and Tutor in Biochemistry at St Edmund Hall, Oxford. www.jansenlab.org
Selected publications
- Ben L Carty, Danilo Dubocanin, Marina Murillo-Pineda, Marie Dumont, Emilia Volpe, Pawel Mikulski, Julia Humes, Oliver Whittingham, Daniele Fachinetti, Simona Giunta, Nicolas Altemose and Lars E.T. Jansen (2025) Heterochromatin boundaries maintain centromere position, size and number. Nature Structural and Molecular Biology, 33: 220-234.
- Pawel Mikulski, Sahar S.H. Tehrani, Anna Kogan, Izma Abdul-Zani, Emer Shell, Brent J. Ryan, Lars E.T. Jansen (2025) Heritable maintenance of chromatin modifications confers transcriptional memory of interferon-γ signaling. Nature Structural & Molecular Biology. 32: 1255-67
- Marina Murillo-Pineda, Luis P. Valente, Marie Dumont, João F. Mata, Daniele Fachinetti and Lars E.T. Jansen (2020) Induction of spontaneous human neocentromere formation and long-term maturation. Journal of Cell Biology,220 (3): e202007210.
- Wojciech Siwek, Sahar S.H. Tehrani, João F. Mata and Lars E.T. Jansen (2020) Activation of clustered IFNγ target genes drives cohesin-controlled transcriptional memory. Molecular Cell, 80: 396-409
- Sreyoshi Mitra, Dani L. Bodor, Ana F. David, Izma Abdul-Zani João F. Mata, Beate Neumann, Sabine Reither, Christian Tischer and Lars E.T. Jansen (2020) Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin. Nature Communications, 11: 501.
- Dragan Stajic, Lília Perfeito and Lars E.T. Jansen (2019) Epigenetic gene silencing alters the mechanisms and rate of evolutionary adaptation. Nature Ecology and Evolution, 3: 491-498.
- Ana Stankovic, Lucie Y. Guo, João F. Mata, Dani L. Bodor, Xing-Jun Cao, Aaron O. Bailey, Jeffrey Shabanowitz, Donald F. Hunt, Benjamin A. Garcia, Ben E. Black and Lars E.T Jansen (2017) A dual inhibitory mechanism sufficient to maintain cell cycle restricted CENP-A assembly. Molecular Cell, 65: 231–246.
- Mariana C.C. Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M.C. Martins, Helfrid Hochegger, Daniel R. Foltz and Lars E.T. Jansen (2012) Cdk activity couples epigenetic centromere inheritance to cell cycle progression. Developmental Cell. 22: 52-63.
Host
Department of Medical Biochemistry and Biophysics (contact: tamsinlindstrom@ki.se)