Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783660471963877376 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7932698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT keenenmadelinem hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT browndavid hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT brennanlucyd hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT rengerroman hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT khooharrison hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT carlsonchristopherr hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT huangbo hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT grillstephanw hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT narlikargeetaj hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains AT reddingsy hp1proteinscompactdnaintomechanicallyandpositionallystablephaseseparateddomains |