In this episode of the Epigenetics Podcast, we caught up with Serena Sanulli from Stanford University to talk about her work on Heterochromatin Protein 1 (HP1), the structure of chromatin on the atomic-scale and the meso-scale, and phase separation.

The Laboratory of Serena Sanulli is interested in finding connections between changes that happen on the nucleosomal level and the resulting impact on chromatin conformation on the meso-scale. They combine methods like NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology and Genetics. This enables them to dissect how cells use the diverse biophysical properties of chromatin to regulate gene expression across length and time scales.

A second focus of the lab is HP1, which interacts with the nucleosome and changes its conformation, enabling the compaction of the genome into heterochromatin, effectively silencing genes in that region. A high concentration of HP1 leads to the phenomenon of phase separation in the nucleus, which the Sanulli lab is now investigating.

References

Sanulli, S., Justin, N., Teissandier, A., Ancelin, K., Portoso, M., Caron, M., Michaud, A., Lombard, B., da Rocha, S. T., Offer, J., Loew, D., Servant, N., Wassef, M., Burlina, F., Gamblin, S. J., Heard, E., & Margueron, R. (2015). Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation. Molecular Cell, 57(5), 769–783. https://doi.org/10.1016/j.molcel.2014.12.020

Sanulli, S., Trnka, M. J., Dharmarajan, V., Tibble, R. W., Pascal, B. D., Burlingame, A. L., Griffin, P. R., Gross, J. D., & Narlikar, G. J. (2019). HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature, 575(7782), 390–394. https://doi.org/10.1038/s41586-019-1669-2

Sanulli, S., & Narlikar, G. J. (2021). Generation and Biochemical Characterization of Phase‐Separated Droplets Formed by Nucleic Acid Binding Proteins: Using HP1 as a Model System. Current Protocols, 1(5). https://doi.org/10.1002/cpz1.109

Related Episodes

Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)

Heterochromatin and Phase Separation (Gary Karpen)

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