Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells

Strickfaden, Hilmar; Tolsma, Thomas O.; Sharma, Ajit; Underhill, D. Alan; Hansen, Jeffrey C.; Hendzel, Michael J.

doi:10.1016/j.cell.2020.11.027

Cited by 222 publications

(267 citation statements)

References 63 publications

Supporting

Mentioning

210

Contrasting

Order By: Relevance

“…Although chromatin mobility seems to be more pronounced in TSA-treated nuclei (Nozaki et al 2017), photobleaching experiments of replication-labeled chromatin clearly argue against a liquid behavior at the mesoscale. Instead, we observed highly constrained mobility over extended periods of time (Strickfaden et al 2020). This gel-like behavior of chromatin did not change after using JQ1, an inhibitor that blocks bromodomain binding to acetylated lysine residues on histone tails (Gibson et al 2019;Strickfaden et al 2020).…”

Section: Physical State Of Chromatinmentioning

confidence: 71%

“…Instead, we observed highly constrained mobility over extended periods of time (Strickfaden et al 2020). This gel-like behavior of chromatin did not change after using JQ1, an inhibitor that blocks bromodomain binding to acetylated lysine residues on histone tails (Gibson et al 2019;Strickfaden et al 2020). Despite the potential reduction of transient crosslinking between chromatin strands caused by bromodomain inhibition, replication foci did not dissolve and photobleached areas did not recover in cells treated with JQ1 (or TSA), suggesting maintenance of a gel-like state.…”

Section: Physical State Of Chromatinmentioning

confidence: 74%

“…1I-1Q), show the ability to transduce force, and its smallest elements (e.g., RDs) do not seem to move freely in interphase (Fig. 2D) (Strickfaden et al 2020).…”

Section: Physical State Of Chromatinmentioning

confidence: 99%

“…PCH can simultaneously serve as a site for LLPS of multiple proteins (such as CBX5, MeCP2, KMT5C, TRIM28, and SUV39H1), which show profoundly different kinetics in FRAP experiments (Erdel et al 2020;Li et al 2020;Strickfaden et al 2019aStrickfaden et al , 2020. It is noteworthy that one protein can even contribute to different kinds of phase separation at the same site.…”

Section: Examples Of Phase Separation In the Nucleusmentioning

confidence: 99%

“…Several groups discussed the possibility for a liquid state of chromatin based on mobility measurements of core histones (Maeshima et al 2015;Nozaki et al 2017), or even observed liquid behavior of aggregates containing reconstituted oligonucleosome chains in vitro (Gibson et al 2019). While Gibson et al tested reconstituted nucleosome arrays in the presence of emulsifying substances (reduced BSA) (Young Lee and Hirose 1992), other recent studies have shown that both reconstituted chromatin and chromatin in vivo behaves more like a solid or hydrogel under physiological conditions at mesoscale dimensions (Strickfaden et al 2020). Maeshima et al (2016) have proposed a liquid model for chromatin at the nanoscale based on following a large number of fluorescent core histone trajectories, each over a short period of time, by single particle tracking.…”

Section: Physical State Of Chromatinmentioning

confidence: 99%

See 4 more Smart Citations

Reflections on the organization and the physical state of chromatin in eukaryotic cells

Strickfaden

2021

Genome

Self Cite

View full text Add to dashboard Cite

In recent years, our perception of chromatin structure and organization in the cell nucleus has changed in fundamental ways. The 30 nm chromatin fiber lost its status as an essential in vivo structure. Hi-C and related biochemical methods, advanced electron and super-resolved fluorescence microscopy, together with concepts from soft matter physics, have revolutionized the field. A comprehensive understanding of the structural and functional interactions that regulate cell-cycle and cell-type-specific nuclear functions appears within reach, but requires integration of top-down and bottom-up approach. In this review, I present an update on nuclear architecture studies with an emphasis on organization and the controversy regarding the physical state of chromatin in cells.

show abstract

Section: Physical State Of Chromatinmentioning

confidence: 71%

Section: Physical State Of Chromatinmentioning

confidence: 74%

“…1I-1Q), show the ability to transduce force, and its smallest elements (e.g., RDs) do not seem to move freely in interphase (Fig. 2D) (Strickfaden et al 2020).…”

Section: Physical State Of Chromatinmentioning

confidence: 99%

Section: Examples Of Phase Separation In the Nucleusmentioning

confidence: 99%

Section: Physical State Of Chromatinmentioning

confidence: 99%

See 3 more Smart Citations

Reflections on the organization and the physical state of chromatin in eukaryotic cells

Strickfaden

2021

Genome

Self Cite

View full text Add to dashboard Cite

show abstract

DNA Droplets: Intelligent, Dynamic Fluid

et al. 2022

View full text Add to dashboard Cite

Figure 1. Overview of DNA droplets as a hybrid from DNA nanotechnology and liquid-liquid phase separation (LLPS) studies. A) DNA droplets, micro-scale condensates of DNA nanostructures (DNA motifs) self-assembled via sticky ends (SEs). A Y-shaped DNA motif (Y-motif) is a branched nanostructure of three single-stranded DNAs (ssDNAs) hybridized to form the branching stems. At the end of each branch, a single-stranded SE protrudes. Two basic features are highlighted: (i) Programmable interactions. DNA droplets favor sequence-specifically selective interactions as encoded in the SE sequences. (ii) Programmability in mechanical properties.The number of the SEs in a single DNA motif, serving as the valency, can be designed to determine the macroscopic rheological properties, including diffusion coefficient and viscoelastic behavior. Adapted with permission. [29]

show abstract

Intracellular Condensates of Oligopeptide for Targeting Lysosome and Addressing Multiple Drug Resistance of Cancer

Wang

Zhang

et al. 2021

Advanced Materials

View full text Add to dashboard Cite

Biomolecular condensates have been demonstrated as a ubiquitous phenomenon in biological systems and play a crucial role in controlling cellular functions. However, the spatiotemporal construction of artificial biomolecular condensates with functions remains challenging and has been less explored. Herein, a general approach is reported to construct biomolecular condensates (e.g., hydrogel) in the lysosome of living cells for cancer therapy and address multiple drug resistance induced by lysosome sequestration. Aromatic‐motif‐appended pH‐responsive hexapeptide (LTP) derived from natural insulin can be uptaken by cancer cells mainly through caveolae‐dependent endocytosis, ensuring the proton‐triggered phase transformation (solution to hydrogel) of LTP inside the lysosome specifically. Lysosomal hydrogelation further leads to enlargement of the lysosome in cancer cells and increases the permeability of the lysosome, resulting in cancer cell death. Importantly, lysosomal assemblies can significantly improve the efficiency of current chemotherapy drugs toward multidrug resistance (MDR) cells in vitro and in xenograft tumor models. As an example of functional artificial condensates in lysosomes, this work provides a new strategy for controlling functional condensates formation precisely in the organelles of living cells and addressing MDR in cancer therapy.

show abstract

Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells

Cited by 222 publications

References 63 publications

Reflections on the organization and the physical state of chromatin in eukaryotic cells

Reflections on the organization and the physical state of chromatin in eukaryotic cells

DNA Droplets: Intelligent, Dynamic Fluid

Intracellular Condensates of Oligopeptide for Targeting Lysosome and Addressing Multiple Drug Resistance of Cancer

Contact Info

Product

Resources

About