Publication Date:
2022-05-26
Description:
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Keenen, M. M., Brown, D., Brennan, L. D., Renger, R., Khoo, H., Carlson, C. R., Huang, B., Grill, S. W., Narlikar, G. J., & Redding, S. HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. Elife, 10, (2021): e64563, https://doi.org/10.7554/eLife.64563.
Description:
In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog’s DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.
Description:
MMK was supported by the Discovery Fellows Program at UCSF and NCI grants F31CA243360 and F99CA245719. RR was support from the NOMIS foundation, Rostock, Germany. BH acknowledges support though NIH R21 GM129652, R01 CA231300 and R01 GM131641. BH is also a Chan Zuckerberg Biohub Investigator. SWG was supported by the DFG (SPP 1782, GSC 97, GR 3271/2, GR 3271/3, GR 3271/4) and the European Research Council (grant 742712). GJN acknowledges support from NIH grant R35 GM127020 and NSF grant 1921794. Support to SR through the UCSF Program for Breakthrough Biomedical Research (PBBR), Sandler Foundation, and Whitman Foundation at the Marine Biological Laboratories.
Repository Name:
Woods Hole Open Access Server
Type:
Article
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