Cargando…
Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation
The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we as...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163299/ https://www.ncbi.nlm.nih.gov/pubmed/32101700 http://dx.doi.org/10.1016/j.molcel.2020.02.005 |
_version_ | 1783523187139543040 |
---|---|
author | Erdel, Fabian Rademacher, Anne Vlijm, Rifka Tünnermann, Jana Frank, Lukas Weinmann, Robin Schweigert, Elisabeth Yserentant, Klaus Hummert, Johan Bauer, Caroline Schumacher, Sabrina Al Alwash, Ahmad Normand, Christophe Herten, Dirk-Peter Engelhardt, Johann Rippe, Karsten |
author_facet | Erdel, Fabian Rademacher, Anne Vlijm, Rifka Tünnermann, Jana Frank, Lukas Weinmann, Robin Schweigert, Elisabeth Yserentant, Klaus Hummert, Johan Bauer, Caroline Schumacher, Sabrina Al Alwash, Ahmad Normand, Christophe Herten, Dirk-Peter Engelhardt, Johann Rippe, Karsten |
author_sort | Erdel, Fabian |
collection | PubMed |
description | The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanistically relevant features of pericentric heterochromatin compaction in mouse fibroblasts. We find that (1) HP1 has only a weak capacity to form liquid droplets in living cells; (2) the size, global accessibility, and compaction of heterochromatin foci are independent of HP1; (3) heterochromatin foci lack a separated liquid HP1 pool; and (4) heterochromatin compaction can toggle between two “digital” states depending on the presence of a strong transcriptional activator. These findings indicate that heterochromatin foci resemble collapsed polymer globules that are percolated with the same nucleoplasmic liquid as the surrounding euchromatin, which has implications for our understanding of chromatin compartmentalization and its functional consequences. |
format | Online Article Text |
id | pubmed-7163299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71632992020-04-22 Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation Erdel, Fabian Rademacher, Anne Vlijm, Rifka Tünnermann, Jana Frank, Lukas Weinmann, Robin Schweigert, Elisabeth Yserentant, Klaus Hummert, Johan Bauer, Caroline Schumacher, Sabrina Al Alwash, Ahmad Normand, Christophe Herten, Dirk-Peter Engelhardt, Johann Rippe, Karsten Mol Cell Article The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanistically relevant features of pericentric heterochromatin compaction in mouse fibroblasts. We find that (1) HP1 has only a weak capacity to form liquid droplets in living cells; (2) the size, global accessibility, and compaction of heterochromatin foci are independent of HP1; (3) heterochromatin foci lack a separated liquid HP1 pool; and (4) heterochromatin compaction can toggle between two “digital” states depending on the presence of a strong transcriptional activator. These findings indicate that heterochromatin foci resemble collapsed polymer globules that are percolated with the same nucleoplasmic liquid as the surrounding euchromatin, which has implications for our understanding of chromatin compartmentalization and its functional consequences. Cell Press 2020-04-16 /pmc/articles/PMC7163299/ /pubmed/32101700 http://dx.doi.org/10.1016/j.molcel.2020.02.005 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Erdel, Fabian Rademacher, Anne Vlijm, Rifka Tünnermann, Jana Frank, Lukas Weinmann, Robin Schweigert, Elisabeth Yserentant, Klaus Hummert, Johan Bauer, Caroline Schumacher, Sabrina Al Alwash, Ahmad Normand, Christophe Herten, Dirk-Peter Engelhardt, Johann Rippe, Karsten Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title | Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title_full | Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title_fullStr | Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title_full_unstemmed | Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title_short | Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation |
title_sort | mouse heterochromatin adopts digital compaction states without showing hallmarks of hp1-driven liquid-liquid phase separation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163299/ https://www.ncbi.nlm.nih.gov/pubmed/32101700 http://dx.doi.org/10.1016/j.molcel.2020.02.005 |
work_keys_str_mv | AT erdelfabian mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT rademacheranne mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT vlijmrifka mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT tunnermannjana mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT franklukas mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT weinmannrobin mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT schweigertelisabeth mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT yserentantklaus mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT hummertjohan mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT bauercaroline mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT schumachersabrina mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT alalwashahmad mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT normandchristophe mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT hertendirkpeter mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT engelhardtjohann mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation AT rippekarsten mouseheterochromatinadoptsdigitalcompactionstateswithoutshowinghallmarksofhp1drivenliquidliquidphaseseparation |