Phase-separation in chromatin organization

2020 ◽  
Vol 45 (1) ◽  
Author(s):  
Geeta J Narlikar
Keyword(s):  
Phase Separation ◽  
Chromatin Organization

scholarly journals Phase separation in transcription factor dynamics and chromatin organization

2021 ◽  
Vol 71 ◽  
pp. 148-155
Author(s):  
Kaustubh Wagh ◽  
David A. Garcia ◽  
Arpita Upadhyaya
Keyword(s):  
Transcription Factor ◽  
Phase Separation ◽  
Chromatin Organization

scholarly journals Quantifying liquid-liquid phase separation property of chromatin under physiological conditions using Hi-MS and Hi-C

2020 ◽  
Author(s):  
Minglei Shi ◽  
Kaiqiang You ◽  
Chao Hou ◽  
Taoyu Chen ◽  
Zhengyu Liang ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Quantitative Measurement ◽  
Biological Process ◽  
Global Analysis ◽  
Chromatin Organization ◽  
Liquid Phase Separation ◽  
Protein Functions ◽  
Associated Proteins ◽  
Liquid Liquid Phase Separation

AbstractBackgroundLiquid–liquid phase separation (LLPS) is an important organizing principle for biomolecular condensation and chromosome compartmentalization. However, while many proteins have been reported to undergo LLPS, quantitative and global analysis of chromatin LLPS property remains absent.ResultsHere, by combing chromatin associated protein pull-down, quantitative proteomics and 1,6-hexanediol treatment, we developed Hi-MS and defined anti-1,6-HD index of chromatin-associated proteins (AICAP) to quantitative measurement of LLPS property of chromatin-associated proteins in their endogenous state and physiological abundance. The AICAP values were verified by previously reported experiments and were reproducible across different MS platforms. Moreover, the AICAP values were highly correlate with protein functions. Proteins act in active/regulatory biological process often exhibit low AICAP values, while proteins act in structural and repressed biological process often exhibit high AICAP values. We further revealed that chromatin organization changes more in compartment A than B, and the changes in chromatin organization at various levels, including compartments, TADs and loops are highly correlated to the LLPS properties of their neighbor nuclear condensates.ConclusionsOur work provided the first global quantitative measurement of LLPS properties of chromatin-associated proteins and higher-order chromatin structure, and demonstrate that the active/regulatory chromatin components, both protein (trans) and DNA (cis), exhibit more hydrophobicity-dependent LLPS properties than the repressed/structural chromatin components.

scholarly journals Chromatin Organization and Phase Separation of Histones

2021 ◽  
Vol 120 (3) ◽  
pp. 278a
Author(s):  
Anisha Shakya ◽  
John King
Keyword(s):  
Phase Separation ◽  
Chromatin Organization

scholarly journals Control of Chromatin Organization and Chromosome Behavior during the Cell Cycle through Phase Separation

2021 ◽  
Vol 22 (22) ◽  
pp. 12271
Author(s):  
Jiaxiang Li ◽  
Jinmin Gao ◽  
Ruoxi Wang
Keyword(s):  
Phase Separation ◽  
Intrinsically Disordered Proteins ◽  
Biological Activities ◽  
Meiotic Chromosome ◽  
Chromatin Organization ◽  
Disordered Proteins ◽  
Chromosome Behavior ◽  
Intrinsically Disordered ◽  
Collective Interactions ◽  
Key Events

Phase-separated condensates participate in various biological activities. Liquid–liquid phase separation (LLPS) can be driven by collective interactions between multivalent and intrinsically disordered proteins. The manner in which chromatin—with various morphologies and activities—is organized in a complex and small nucleus still remains to be fully determined. Recent findings support the claim that phase separation is involved in the regulation of chromatin organization and chromosome behavior. Moreover, phase separation also influences key events during mitosis and meiosis. This review elaborately dissects how phase separation regulates chromatin and chromosome organization and controls mitotic and meiotic chromosome behavior.

scholarly journals In Diverse Conditions Intrinsic Chromatin Condensates Have Liquid-like Material Properties

2021 ◽  
Author(s):  
Bryan A Gibson ◽  
Claudia Blaukopf ◽  
Tracy Lou ◽  
Lynda K Doolittle ◽  
Ilya J Finkelstein ◽  
...  
Keyword(s):  
Phase Separation ◽  
Sample Preparation ◽  
Recent Work ◽  
Material Properties ◽  
Nuclear Dna ◽  
Chromatin Organization ◽  
Physical Mechanisms ◽  
Cellular Factors ◽  
Intrinsic Capacity

Eukaryotic nuclear DNA is wrapped around histone proteins to form nucleosomes, which further assemble to package and regulate the genome. Understanding of the physical mechanisms that contribute to higher order chromatin organization is limited. Previously, we reported the intrinsic capacity of chromatin to undergo phase separation and form dynamic liquid-like condensates, which can be regulated by cellular factors. Recent work from Hansen, Hendzel, and colleagues suggested these intrinsic chromatin condensates are solid in all but a specific set of conditions. Here we show that intrinsic chromatin condensates are fluid in diverse solutions, without need for specific buffering components. Exploring experimental differences in sample preparation and imaging between these two studies, we suggest what may have led Hansen, Hendzel, and colleagues to mischaracterize the innate properties of chromatin condensates. We also describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained movement of chromatin in cells.

scholarly journals Chromatin organization by an interplay of loop extrusion and compartmental segregation

2018 ◽  
Vol 115 (29) ◽  
pp. E6697-E6706 ◽  
Author(s):  
Johannes Nuebler ◽  
Geoffrey Fudenberg ◽  
Maxim Imakaev ◽  
Nezar Abdennur ◽  
Leonid A. Mirny
Keyword(s):  
Gene Regulation ◽  
Phase Separation ◽  
Chromatin Organization ◽  
Chromosome Organization ◽  
Chromatin States ◽  
Topologically Associating Domains ◽  
Special Cases ◽  
Active Mixing ◽  
Differential Attraction ◽  
Inactive Chromatin

Mammalian chromatin is spatially organized at many scales showing two prominent features in interphase: (i) alternating regions (1–10 Mb) of active and inactive chromatin that spatially segregate into different compartments, and (ii) domains (<1 Mb), that is, regions that preferentially interact internally [topologically associating domains (TADs)] and are central to gene regulation. There is growing evidence that TADs are formed by active extrusion of chromatin loops by cohesin, whereas compartmentalization is established according to local chromatin states. Here, we use polymer simulations to examine how loop extrusion and compartmental segregation work collectively and potentially interfere in shaping global chromosome organization. A model with differential attraction between euchromatin and heterochromatin leads to phase separation and reproduces compartmentalization as observed in Hi-C. Loop extrusion, essential for TAD formation, in turn, interferes with compartmentalization. Our integrated model faithfully reproduces Hi-C data from puzzling experimental observations where altering loop extrusion also led to changes in compartmentalization. Specifically, depletion of chromatin-associated cohesin reduced TADs and revealed finer compartments, while increased processivity of cohesin strengthened large TADs and reduced compartmentalization; and depletion of the TAD boundary protein CTCF weakened TADs while leaving compartments unaffected. We reveal that these experimental perturbations are special cases of a general polymer phenomenon of active mixing by loop extrusion. Our results suggest that chromatin organization on the megabase scale emerges from competition of nonequilibrium active loop extrusion and epigenetically defined compartment structure.

scholarly journals A charge-dependent phase transition determines interphase chromatin organization

2019 ◽  
Author(s):  
Hilmar Strickfaden ◽  
Ajit K. Sharma ◽  
Michael J. Hendzel
Keyword(s):  
Phase Transition ◽  
Phase Separation ◽  
Environmental Changes ◽  
Spectroscopic Imaging ◽  
Cell Types ◽  
Chromatin Organization ◽  
Electron Spectroscopic Imaging ◽  
Mammalian Cell Lines ◽  
Interchromatin Compartment

AbstractAn emerging principle of cellular compartmentalization is that liquid unmixing results in formation of compartments by phase separation. We used electron spectroscopic Imaging (ESI), a transmission electron microscopy technology, to distinguish chromatin and nucleoplasmic phases of mammalian cell lines and their responses towards different environmental changes. We tested the hypothesis that charge-dependent phase separation mediated by the histone N-termini could explain the organization of chromatin. 3D images of nuclear chromatin with electron spectroscopic imaging (ESI) demonstrates that the amount of chromatin proximal to the interchromatin compartment (IC) differs between cell types, reflecting major differences in chromatin organization. These differences were lost when cells were treated overnight with a histone deacetylase inhibitor. We show that drastic, reversible changes in chromatin mixing or unmixing with the nucleoplasm/interchromatin space can be induced by modulating osmolarity of the medium or acetylation status of the chromatin. In vitro phase separation experiments demonstrated that chromatin separated from solution through a phase transition towards a more solid chromatin state.

scholarly journals Protein phase separation and its role in chromatin organization and diseases

2021 ◽  
Vol 138 ◽  
pp. 111520
Author(s):  
Jiaqi Li ◽  
Yao Zhang ◽  
Xi Chen ◽  
Lijuan Ma ◽  
Pilong Li ◽  
...  
Keyword(s):  
Phase Separation ◽  
Chromatin Organization
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