HP1 proteins compact DNA into mechanically and positionally stable phase separated domains

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.

doi:10.1101/2020.10.30.362772

bioRxiv · 10.1101/2020.10.30.362772

HP1 proteins compact DNA into mechanically and positionally stable phase separated domains

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.

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Abstract

In mammals HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1, HP1{beta}, and HP1{gamma}, 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 HP1-DNA condensates, HP1 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 HP1{beta}. Finally, we find that differences in each HP1 paralogs 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.

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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.. 2020-10-31. HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. https://doi.org/10.1101/2020.10.30.362772

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