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What is the evidence against LLPS as the mechanism of nuclear body formation? 


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Liquid-liquid phase separation (LLPS) has been extensively studied as a mechanism underlying the formation of nuclear bodies and other membraneless organelles within the cell nucleus. However, evidence against LLPS as the sole mechanism for nuclear body formation emerges from various studies, highlighting the complexity of nuclear organization and the potential involvement of alternative mechanisms. Firstly, while LLPS is recognized for its role in the assembly of nuclear bodies, certain nuclear structures do not align with key predictions of LLPS, suggesting that other mechanisms may contribute to nuclear organization. This discrepancy indicates that the behavior of some nuclear compartments cannot be fully explained by LLPS alone. Additionally, the dynamic regulation of chromatin states, which can exist in solid- or liquid-like forms, is influenced by a range of factors beyond LLPS, including ions, binding proteins, and post-translational modifications. This complexity suggests that LLPS is part of a broader spectrum of mechanisms governing chromatin organization and nuclear body formation. Moreover, the treatment of cells with 1,6-hexanediol, which disrupts LLPS, resulted in changes in chromatin organization that did not fully revert upon removal of the treatment. This outcome implies that LLPS may play a limited role in maintaining the spatial organization of chromatin, and that other factors are involved in establishing and preserving the structure of nuclear compartments. Furthermore, the mechanical properties of LLPS domains, as demonstrated by the role of Swi6 in contributing to nuclear stiffness, suggest that the physical characteristics of phase-separated domains have functional implications beyond simple compartmentalization. In summary, while LLPS is a significant factor in the formation of nuclear bodies, evidence suggests that it is not the sole mechanism. Alternative processes, including protein-nucleic acid interactions and the mechanical properties of chromatin, also play crucial roles in nuclear organization.

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1,6-Hexanediol treatment disrupts LLPS, leading to altered chromatin organization, weakened enhancer-promoter interactions, and compromised TAD insulation, suggesting limited involvement of LLPS in nuclear body formation.
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Open accessJournal ArticleDOI
Peng A, Stephanie C. Weber 
01 Nov 2019-Non-Coding RNA
121 Citations
The evidence against LLPS for nuclear body formation includes discrepancies in behavior of certain structures like paraspeckles and RCs, supporting alternative models like the bridging model.
Not addressed in the paper.
Evidence against LLPS as the mechanism of nuclear body formation is the crippled LLPS in PML A216V and Leu to Pro mutations affecting coiled-coil domain, leading to altered PML packing.
Evidence against LLPS as the mechanism of nuclear body formation is the crippled LLPS in PML A216V and Leu to Pro mutations, affecting PML NB assembly and function.

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