| Researchers at the Laboratoire de Physique des Solides (LPS) have directly observed the organization of chromatin at the core of cells in Drosophila embryos, in a state close to that of living systems. Using a cryo-electron tomography approach, they revealed a DNA structure that is far more disordered and dynamic than classical models had suggested, with highly variable nucleosomes and irregular folding of the filament. They also identified atypical nucleosome forms, likely linked to gene activity. These findings provide new insight into how DNA is organized and regulated within the cell. |
In most eukaryotic chromosomes, DNA is organized as a “beads-on-a-string” chain of nucleosomes connected by linker DNA segments. This fundamental organization was described more than fifty years ago, yet its actual in situ architecture remains largely unknown.
To address this question, we developed a cryo-electron tomography approach applied to vitreous sections of Drosophila embryos frozen in their native state. This experimental system makes it possible to target different functional compartments of chromatin, thanks to the characteristic segregation of large compact domains of constitutive heterochromatin in these embryos.
We were thus able to visualize and analyze the DNA filament wrapped around nucleosomes and linking them together. Our analyses reveal a disordered zig-zag folding, characterized by linker DNA with highly variable lengths and low curvature, with little difference between functional compartments. The nucleosomes themselves display significant conformational variability, including open, closed, and gaping states. These findings confirm and refine the previously proposed dynamic “liquid chromatin” model.
Finally, we identified different types of particles exhibiting variable amounts of DNA wrapped around their surface, ranging from less than one turn to three turns, whereas the canonical nucleosome corresponds to about 1.7 turns. These particles, consistent with the in situ presence of tetrasomes, hemisomes, hexasomes, and overlapping dinucleosomes, are localized in nanodomains dispersed throughout the nucleoplasm—corresponding to regions of euchromatin and/or facultative heterochromatin—rather than within compact domains of constitutive heterochromatin. The existence of such particles had been theoretically predicted or indirectly suggested in connection with transcription.
This pioneering work demonstrates the potential of cryo-electron tomography to study the functional organization of chromosomes in situ, within whole organisms. By targeting different functional compartments of chromatin in interphase, it opens the way to a better understanding of the link between structural organization and functional state. In particular, sub-nucleosome and super-nucleosome–like particles may correspond to intermediate transcriptional states, providing new insight into the molecular basis of gene expression regulation.
Financements
ANR CRYOCHROM (ANR-20-CE11-0020), FRISBI (French Infrastructure for Integrated Structural Biology, ANR-10-INSB-005) et iNext Discovery (EC H2020).
Références
Fatmaoui, F., Carrivain, P., Taiki, F. et al. Direct visualization and tracing of chromatin folding in the Drosophila embryo. EMBO J (2026). https://doi-org.ezproxy.universite-paris-saclay.fr/10.1038/s44318-026-00701-7
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