Heterochromatin Formation by the HUSH complex (Iva Tchasovnikarova)

In this episode of the Epigenetics Podcast, we talked with Iva Tchasovnikarova from the Wellcome Trust Cancer Research UK Gurdon Institute about her work on heterochromatin formation and epigenetic control.

We begin with Dr. Tchasovnikarova's journey into the field of biology, tracing her roots back to her formative years and the pragmatic guidance of her parents. Despite initial uncertainty about her career path, it was her mother’s passion for teaching biology that ultimately inspired her to pursue a degree in the subject.

As Dr. Tchasovnikarova introduces her current role as a group leader at the Gurdon Institute and an assistant professor at the University of Cambridge, she highlights her early work during her PhD which yielded a first-author publication in Science. She reflects on the serendipitous aspects of this experience, detailing a project where she utilised a novel genetic screening system to uncover a repressor complex named HUSH, a pivotal discovery that has implications for understanding transcriptional repression mechanisms in vertebrates.

The conversation progresses into her postdoctoral research, where she further explored the HUSH complex's role alongside another complex, HUSH2. This expansion of her research reveals fascinating insights into how these complexes interact and their potential significance in regulating gene expression, particularly concerning immune responses to viral infections. Dr. Tchasovnikarova outlines her systematic approach to unraveling these complexities, emphasizing the role of reporter systems and genetic screens in uncovering uncharacterized genes and their functions.

In discussing her transition to starting her own lab, Dr. Tchasovnikarova shares her excitement about utilizing methods she developed during her postdoc to discover new regulatory mechanisms. She describes specific experiments that have led to groundbreaking findings, including the characterization of CRAMP1, a regulator of linker histones, which plays a crucial role in the function of the polycomb repressive complex. The intricate relationships between these elements underscore her commitment to understanding the nuances of epigenetic regulation and genome stability.

References

• Tchasovnikarova, I. A., Timms, R. T., Matheson, N. J., Wals, K., Antrobus, R., Göttgens, B., Dougan, G., Dawson, M. A., & Lehner, P. J. (2015). GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science (New York, N.Y.), 348(6242), 1481–1485. https://doi.org/10.1126/science.aaa7227
• Danac, J. M. C., Matthews, R. E., Gungi, A., Qin, C., Parsons, H., Antrobus, R., Timms, R. T., & Tchasovnikarova, I. A. (2024). Competition between two HUSH complexes orchestrates the immune response to retroelement invasion. Molecular cell, 84(15), 2870–2881.e5. https://doi.org/10.1016/j.molcel.2024.06.020

Related Episodes

• Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli)
• Heterochromatin and Phase Separation (Gary Karpen)
• Polycomb and Three-Dimensional Genome Organisation (Oliver Bell)

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