HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
| Autor: | Madeline M. Keenen, Sy Redding, Harrison Khoo, Geeta J. Narlikar, Lucy D Brennan, Bo Huang, David Brown, Christopher R. Carlson, Stephan W. Grill, Roman Renger |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Chromosomal Proteins Non-Histone Structural Biology and Molecular Biophysics metabolism [Chromobox Protein Homolog 5] chemistry.chemical_compound 0302 clinical medicine structural biology Biology (General) Cells Cultured Genomic organization chemistry.chemical_classification General Neuroscience General Medicine Polymer genetics [Chromobox Protein Homolog 5] Medicine metabolism [Chromosomal Proteins Non-Histone] Research Article Human Protein Binding animal structures QH301-705.5 Heterochromatin Science Chemical biology chemical biology genetics [Chromosomal Proteins Non-Histone] General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Biochemistry and Chemical Biology molecular biophysics Humans biochemistry human General Immunology and Microbiology fungi Molecular biophysics heterochromatin DNA metabolism [Heterochromatin] 030104 developmental biology Structural biology chemistry Chromobox Protein Homolog 5 Biophysics metabolism [DNA] Heterochromatin protein 1 phase separation ddc:600 030217 neurology & neurosurgery chromatin organization |
| Zdroj: | eLife 10, e64563 (2021). doi:10.7554/eLife.64563 eLife eLife, Vol 10 (2021) |
| DOI: | 10.7554/eLife.64563 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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