Biology subjects

Quail, T.

Publications and source records attributed to Quail, T..

4 recordsLinked to original sources

bioRxiv2025

Cryo-EM reveals open and closed Asgard chromatin assemblies

Asgards are the closest archaeal relatives of eukaryotes, representing an important step in chromatin evolution. However, their chromatin organization has remained enigmatic until now. In this study, we present the first structures of Asgard chromatin assemblies formed by the Hodarchaeal histone HHoB. Our high-resolution cryo-EM structures reveal that this Asgard histone assembles into compact "closed" and into extended "open" hypernucleosomes. Thus the closed hypernucleosome conformation is conserved across archaeal lineages, while the open conformation resembles a eukaryotic H3-H4 octasome and likely represents an Asgard- specific innovation. Moreover, we show that Mg{superscript 2} ions influence Asgard chromatin conformation, suggesting a regulatory role. Overall, our study provides the first structure-based model of Asgard chromatin organization, expanding our understanding of chromatin architecture in evolutionary context.

biophysics↗

bioRxiv2024

Nuclear partitioning by surface condensation on metaphase chromatids

Protein partitioning between the nucleus and the cytoplasm is a defining feature of eukaryotic cells, and it is thought to be primarily regulated by transport across the nuclear envelope1-3. However, during early vertebrate development, ensuring accurate nuclear composition is challenging due to dramatic changes in cell size and rapid cell division4-7. Here, we show that the embryonic linker histone H1.8 is rapidly partitioned into the nucleus through a nuclear import-independent mechanism. In the cytoplasm of Xenopus laevis egg extracts, prior to nuclear assembly, H1.8 condenses on the surface of chromatids as droplets that partially wet them. Simultaneously, H1.8 also forms condensates in the cytoplasm that buffer the condensate nucleation rate on the chromatid surface, resulting in a nuclear partitioning that is independent of the DNA-to-cytoplasm ratio. To show the generality of the surface condensation mechanism, we extended our study to Nucleophosmin 1 (NPM1) in human cell culture. Similar to H1.8, NPM1 forms a layer around chromatids that breaks into droplets that subsequently are incorporated into the nucleus. Our findings show that the properties of condensate wetting and nucleation on chromatid surfaces provide an alternative and robust biophysical mechanism to regulate nuclear composition.

biophysics↗

bioRxiv2020

Capillary forces drive pioneer transcription factor-mediated DNA condensation

Interactions between liquids and surfaces generate forces1,2 that are crucial for many processes in biology, physics, and engineering, including the motion of insects on the surface of water3, modulation of the material properties of spider silk4, and self-assembly of microstructures5. Recent studies have shown that cells assemble biomolecular condensates via phase separation6. In the nucleus, these condensates are thought to drive transcription7, heterochromatin formation8, nucleolus assembly9, and DNA repair10. Here, we show that the interaction between liquid-like condensates and DNA generates forces that might play a role in bringing distant regulatory elements of DNA together, a key step in transcriptional regulation. We combine quantitative microscopy, in vitro reconstitution, optical tweezers, and theory to show that the transcription factor FoxA1 mediates the condensation of a DNA-protein phase via a mesoscopic first- order phase transition. After nucleation, co-condensation forces drive growth of this phase by pulling non-condensed DNA. Altering the tension on the DNA strand enlarges or dissolves the condensates, revealing their mechanosensitive nature. These findings show that DNA condensation mediated by transcription factors could bring distant regions of DNA in close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.

biophysics↗

bioRxiv2019

Cohesin and condensin extrude loops in a cell-cycle dependent manner

Chromatin undergoes a dramatic reorganization during the cell cycle1-3. In interphase, chromatin is organized into compartments and topological-associating domains (TADs) that are cell-type specific4-7, whereas in metaphase, chromosomes undergo large-scale compaction, leading to the loss of specific boundaries and the shutdown of transcription8-12. Loop extrusion by structural maintenance of chromosomes complexes (SMCs) has been proposed as a mechanism to organize chromatin in interphase and metaphase13-19. However, the requirements for chromatin organization in these cell phases are very different, and it is unknown whether loop extrusion dynamics and the complexes that extrude them also differ. Here, we used Xenopus egg extracts to reconstitute and image loop extrusion of single DNA molecules during the cell cycle. We show that loops form in both metaphase and interphase, but with distinct dynamic properties. Condensin extrudes asymmetric loops in metaphase, whereas cohesin extrudes symmetric loops in interphase. Our data show that loop extrusion is a general mechanism for the organization of DNA, with dynamic and structural properties that are molecularly regulated during the cell cycle.

cell biology↗