The rise and fall of the 30 nm fiber

Although the structure of the nucleosome has been solved with atomic resolution, higher-order structures of chromatin remain ill-defined and are still controversial. It was book knowledge for ages – and I was also told so in my own biochemistry lectures – that nucleosomes (i.e. the beads-on-a string structure or the 10 nm fiber) fold and assemble into higher order structures until chromosome-level of compaction is achieved. In this model, the 30 nm fiber represents the next level of compaction. Strikingly, there is now an increasing body of evidence that such a 30 nm fiber might not exist at all! Attempts to visualize distinct 30 nm fibers in vivo completely failed so far except for very specialized, mostly transcriptionally inactive cell types (such as chicken erythrocytes). Highly sophisticated methods including small angle X-ray scattering (SAXS),Cryo-EM, and electron spectroscopic imaging revealed no regular chromatin structures beyond the 10 nm fiber. Irregular groups of nucleosomes – “nucleosome clutches” – were observed in chromatin fibers by super-resolution microscopyand disordered chains formed by nucleosomes in human interphase and mitotic cells by ChromEMT (which combines electron microscopy tomography with a labeling method enhancing the contrast for DNA). Thus, the paradigm is currently changing: New models assume that more compact chromatin domains are built from the self-interacting properties of the 10 nm fiber. Nucleosomes likely interact and interdigitate extensively with distant nucleosomes or nucleosomes of distinct 10 nm fibers resulting in globular domains. But what about the findings by Finch and Klug in 1976 that clearly showed that isolated nucleosome fibers do form in vitro structures with a diameter of roughly 30 nm? It could be that the 30 nm chromatin fiber only exists transiently or is only formed under certain circumstances such as terminal differentiation. Or this was all just an in vitro artefact 😉

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