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

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. Us...

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Autores principales: Keenen, Madeline M, Brown, David, Brennan, Lucy D, Renger, Roman, Khoo, Harrison, Carlson, Christopher R, Huang, Bo, Grill, Stephan W, Narlikar, Geeta J, Redding, Sy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932698/
https://www.ncbi.nlm.nih.gov/pubmed/33661100
http://dx.doi.org/10.7554/eLife.64563
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author Keenen, Madeline M
Brown, David
Brennan, Lucy D
Renger, Roman
Khoo, Harrison
Carlson, Christopher R
Huang, Bo
Grill, Stephan W
Narlikar, Geeta J
Redding, Sy
author_facet Keenen, Madeline M
Brown, David
Brennan, Lucy D
Renger, Roman
Khoo, Harrison
Carlson, Christopher R
Huang, Bo
Grill, Stephan W
Narlikar, Geeta J
Redding, Sy
author_sort Keenen, Madeline M
collection PubMed
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.
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spelling pubmed-79326982021-03-08 HP1 proteins compact DNA into mechanically and positionally stable phase separated domains Keenen, Madeline M Brown, David Brennan, Lucy D Renger, Roman Khoo, Harrison Carlson, Christopher R Huang, Bo Grill, Stephan W Narlikar, Geeta J Redding, Sy eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2021-03-04 /pmc/articles/PMC7932698/ /pubmed/33661100 http://dx.doi.org/10.7554/eLife.64563 Text en © 2021, Keenen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Keenen, Madeline M
Brown, David
Brennan, Lucy D
Renger, Roman
Khoo, Harrison
Carlson, Christopher R
Huang, Bo
Grill, Stephan W
Narlikar, Geeta J
Redding, Sy
HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title_full HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title_fullStr HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title_full_unstemmed HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title_short HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
title_sort hp1 proteins compact dna into mechanically and positionally stable phase separated domains
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932698/
https://www.ncbi.nlm.nih.gov/pubmed/33661100
http://dx.doi.org/10.7554/eLife.64563
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