Title | Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Eeftens, JM, Kapoor, M, Michieletto, D, Brangwynne, CP |
Journal | Nat Commun |
Volume | 12 |
Issue | 1 |
Pagination | 5888 |
Date Published | 2021 10 07 |
ISSN | 2041-1723 |
Keywords | Cell Cycle Proteins, Chromatin, Chromatin Assembly and Disassembly, Epigenesis, Genetic, HEK293 Cells, Heterochromatin, Histones, Humans, Microtubule-Associated Proteins, Polycomb Repressive Complex 1, Polycomb-Group Proteins, Ubiquitination |
Abstract | <p>Organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Phase-separation has been implicated in heterochromatin formation, but it is unclear how phase-separated condensates can contribute to stable repression, particularly for heritable epigenetic changes. Polycomb complex PRC1 is key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we show that PRC1 forms multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. We show that inducing Polycomb phase-separation can cause chromatin compaction, but polycomb condensates are dispensable for maintenance of the compacted state. Our data and simulations are consistent with a model in which the time integral of Polycomb phase-separation is progressively recorded in repressive histone marks, which subsequently drive compaction. These findings link the equilibrium thermodynamics of phase-separation with the fundamentally non-equilibrium concept of epigenetic memory.</p> |
DOI | 10.1038/s41467-021-26147-5 |
Alternate Journal | Nat Commun |
PubMed ID | 34620850 |
PubMed Central ID | PMC8497513 |
Grant List | U01 DA040601 / DA / NIDA NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States |