HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
Madeline M. Keenen,David Brown,Lucy D Brennan,Roman Renger,Harrison Khoo,Christopher R. Carlson,Bo Huang,Stephan W. Grill,Stephan W. Grill,Geeta J. Narlikar,Sy Redding,Sy Redding +11 more
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TLDR
In this article, the phase-separation by HP1 proteins can explain the biological properties of HP1-mediated heterochromatin, and the authors 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.Abstract:
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.read more
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Mechanics and functional consequences of nuclear deformations
TL;DR: In this article , the physical connections from chromatin to nuclear lamina and cytoskeletal filaments are considered as a single mechanical unit, and a critical review of the structural and functional adaptive responses of the nucleus to deformations is provided.
Journal ArticleDOI
Phase Separation in Genome Organization across Evolution
Marina Feric,Tom Misteli +1 more
TL;DR: In this paper, the role of phase separation in genome organization across the evolutionary spectrum from bacteria to mammals is discussed, suggesting that molecular interactions among DNA-binding proteins evolved to form a variety of biomolecular condensates with distinct material properties that affect genome organization and function.
Journal ArticleDOI
Hp1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics
Amy R. Strom,Ronald J Biggs,Edward J. Banigan,Xiaotao Wang,Katherine Chiu,Cameron Herman,Jimena Collado,Feng Yue,Joan C. Ritland Politz,Leah J Tait,David Scalzo,Agnes Telling,Mark Groudine,Clifford P. Brangwynne,John F. Marko,Andrew D. Stephens +15 more
TL;DR: In this paper, the authors used a novel HP1α auxin-inducible degron human cell line to rapidly degrade HP 1α (CBX5) and found that HP 1 α is essential to chromatin-based mechanics and maintains nuclear morphology.
Journal ArticleDOI
Capillary forces generated by biomolecular condensates
Bernardo Gouveia,Yoonji Kim,Joshua W. Shaevitz,Sabine Petry,Howard A. Stone,Clifford P. Brangwynne +5 more
TL;DR: The physical principles of capillarity are presented, including examples of how capillary forces structure multiphase condensates and remodel biological substrates.
Journal ArticleDOI
Membrane surfaces regulate assembly of ribonucleoprotein condensates
TL;DR: In this article , the authors examined how membrane association affects condensate size in the endoplasmic reticulum and found that membrane recruitment promotes condensation under physiological conditions.
References
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Biomolecular condensates: organizers of cellular biochemistry
TL;DR: This work has shown that liquid–liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates and has proposed a physical framework for this organizing principle.
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Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
Andrew J. Bannister,Philip Zegerman,Janet F. Partridge,Eric A. Miska,Jean O. Thomas,Robin C. Allshire,Tony Kouzarides +6 more
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.
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Phase transitions in the assembly of multivalent signalling proteins
Pilong Li,Sudeep Banjade,Hui-Chun Cheng,Soyeon Kim,Baoyu Chen,Liang Guo,Marc C. Llaguno,Javoris Hollingsworth,David S. King,Salman F. Banani,Paul S. Russo,Qiu-Xing Jiang,B. Tracy Nixon,Michael K. Rosen +13 more
TL;DR: Interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid–liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution.
Journal ArticleDOI
Coexisting Liquid Phases Underlie Nucleolar Subcompartments
Marina Feric,Nilesh Vaidya,Tyler S. Harmon,Diana M. Mitrea,Lian Zhu,Tiffany M. Richardson,Richard W. Kriwacki,Rohit V. Pappu,Clifford P. Brangwynne +8 more
TL;DR: It is shown that subcompartments within the nucleolus represent distinct, coexisting liquid phases that may facilitate sequential RNA processing reactions in a variety of RNP bodies, and suggested that phase separation can give rise to multilayered liquids.