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Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin
Gene silencing by heterochromatin is proposed to occur in part from the ability of HP1 proteins to spread across large regions of the genome, compact the underlying chromatin and recruit repressive activities(1–3). Here we identify a new property of the human HP1α protein: the ability to form phase-...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606208/ https://www.ncbi.nlm.nih.gov/pubmed/28636604 http://dx.doi.org/10.1038/nature22822 |
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author | Larson, Adam G. Elnatan, Daniel Keenen, Madeline M. Trnka, Michael J. Johnston, Jonathan B. Burlingame, Alma L. Agard, David A. Redding, Sy Narlikar, Geeta J. |
author_facet | Larson, Adam G. Elnatan, Daniel Keenen, Madeline M. Trnka, Michael J. Johnston, Jonathan B. Burlingame, Alma L. Agard, David A. Redding, Sy Narlikar, Geeta J. |
author_sort | Larson, Adam G. |
collection | PubMed |
description | Gene silencing by heterochromatin is proposed to occur in part from the ability of HP1 proteins to spread across large regions of the genome, compact the underlying chromatin and recruit repressive activities(1–3). Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation driven phase-separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets but other molecules such as the transcription factor TFIIB show no preference. Using single-molecule DNA curtains we find that unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, though with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands based on nuclear context. |
format | Online Article Text |
id | pubmed-5606208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-56062082017-12-21 Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin Larson, Adam G. Elnatan, Daniel Keenen, Madeline M. Trnka, Michael J. Johnston, Jonathan B. Burlingame, Alma L. Agard, David A. Redding, Sy Narlikar, Geeta J. Nature Article Gene silencing by heterochromatin is proposed to occur in part from the ability of HP1 proteins to spread across large regions of the genome, compact the underlying chromatin and recruit repressive activities(1–3). Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation driven phase-separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets but other molecules such as the transcription factor TFIIB show no preference. Using single-molecule DNA curtains we find that unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, though with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands based on nuclear context. 2017-06-21 2017-07-13 /pmc/articles/PMC5606208/ /pubmed/28636604 http://dx.doi.org/10.1038/nature22822 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Larson, Adam G. Elnatan, Daniel Keenen, Madeline M. Trnka, Michael J. Johnston, Jonathan B. Burlingame, Alma L. Agard, David A. Redding, Sy Narlikar, Geeta J. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title | Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title_full | Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title_fullStr | Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title_full_unstemmed | Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title_short | Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin |
title_sort | liquid droplet formation by hp1α suggests a role for phase separation in heterochromatin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606208/ https://www.ncbi.nlm.nih.gov/pubmed/28636604 http://dx.doi.org/10.1038/nature22822 |
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