Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Epigenetic memory as a time integral over prior history of Polycomb phase separation

Jorine M. Eeftens, Manya Kapoor, Clifford P. Brangwynne
doi: https://doi.org/10.1101/2020.08.19.254706
Jorine M. Eeftens
1Department of Chemical and Biological Engineering, Princeton University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manya Kapoor
1Department of Chemical and Biological Engineering, Princeton University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clifford P. Brangwynne
1Department of Chemical and Biological Engineering, Princeton University
2The Howard Hughes Medical Institute
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: cbrangwy@princeton.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Structural organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Heterochromatin is a more compact form of chromatin, and is associated with characteristic post-translational histone modifications and chromatin binding proteins. Phase-separation has recently been suggested as a mechanism for heterochromatin formation, through condensation of heterochromatin associated proteins. However, it is unclear how phase-separated condensates can contribute to stable and robust repression, particularly for heritable epigenetic changes. The Polycomb complex PRC1 is known to be key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we take a quantitative live cell imaging approach to show that PRC1 proteins form multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. Using optogenetics to nucleate local Polycomb condensates, we show that Polycomb phase separation can induce chromatin compaction, but phase separation is dispensable for maintenance of the compacted state. Our data are consistent with a model in which the time integral of historical Polycomb phase separation is progressively recorded in repressive histone marks, which subsequently drive chromatin compaction. These findings link the equilibrium thermodynamics of phase separation with the fundamentally non-equilibrium concept of epigenetic memory.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 19, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Epigenetic memory as a time integral over prior history of Polycomb phase separation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Epigenetic memory as a time integral over prior history of Polycomb phase separation
Jorine M. Eeftens, Manya Kapoor, Clifford P. Brangwynne
bioRxiv 2020.08.19.254706; doi: https://doi.org/10.1101/2020.08.19.254706
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Epigenetic memory as a time integral over prior history of Polycomb phase separation
Jorine M. Eeftens, Manya Kapoor, Clifford P. Brangwynne
bioRxiv 2020.08.19.254706; doi: https://doi.org/10.1101/2020.08.19.254706

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3505)
  • Biochemistry (7346)
  • Bioengineering (5323)
  • Bioinformatics (20263)
  • Biophysics (10016)
  • Cancer Biology (7743)
  • Cell Biology (11300)
  • Clinical Trials (138)
  • Developmental Biology (6437)
  • Ecology (9951)
  • Epidemiology (2065)
  • Evolutionary Biology (13322)
  • Genetics (9361)
  • Genomics (12583)
  • Immunology (7701)
  • Microbiology (19021)
  • Molecular Biology (7441)
  • Neuroscience (41036)
  • Paleontology (300)
  • Pathology (1229)
  • Pharmacology and Toxicology (2137)
  • Physiology (3160)
  • Plant Biology (6860)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1896)
  • Systems Biology (5311)
  • Zoology (1089)