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Abstract The formation of condensed heterochromatin is critical for establishing cell-specific transcriptional programs. To reveal structural transitions underlying heterochromatin formation in maturing mouse rod photoreceptors, we apply cryo-electron microscopy (cryo-EM) tomography, AI-assisted denoising, and molecular modeling. We find that chromatin isolated from immature retina cells contains many closely apposed nucleosomes with extremely short or absent nucleosome linkers, which are inconsistent with the typical two-start zigzag chromatin folding. In mature retina cells, the fraction of short-linker nucleosomes is much lower, supporting stronger chromatin compaction. By cryo-EM-assisted nucleosome interaction capture, we observe that chromatin in immature retina is enriched with i ± 1 interactions, while chromatin in mature retina contains predominantly i ± 2 interactions typical of the two-start zigzag. By mesoscale modeling and computational simulation, we clarify that the unusually short linkers typical of immature retina are sufficient to inhibit the two-start zigzag and chromatin compaction by the interference of very short linkers with linker DNA stems. We propose that this short linker composition renders nucleosome arrays more open in immature retina and that, as the linker DNA length increases in mature retina, chromatin becomes globally condensed via tight zigzag folding. This mechanism may be broadly utilized to introduce higher chromatin folding entropy for epigenomic plasticity. 

Macromolecular architecture is a critical parameter when tuning polymer material properties. Although the implementation of non-linear polymers in different applications has grown over the years, polymer grafted surfaces such as nanoparticles have traditionally been composed of linear thermoplastic polymers, with a limited number of examples demonstrating a diversity in polymer architectures. In an effort to combine polymer architecturally dependent material properties with polymer grafted particles (PGPs), as opposed to conventional methods of tuning polymer grafting parameters such as the number of chains per surface area (i.e., polymer graft density), a series of bottlebrush grafted particles were synthesized using surface-initiated ring-opening metathesis polymerization (SI-ROMP). These bottlebrush PGPs are composed of glassy, semi-crystalline, and elastomeric polymer side chains with controlled backbone degrees of polymerization (Nbb) at relatively constant polymer graft density on the surface of silica particles with diameters equaling approximately 160 or 77 nm. Bottlebrush polymer chain conformations, evaluated by measuring the brush height of surface grafted polymer chains in solution and the melt, undergo drastic changes in macromolecular dimensions in different environments. In solution, brush heights increase linearly as a function of Nbb, consistent with fully stretched chains, which is confirmed using cryogenic transmission electron microscopy (Cryo-TEM). Meanwhile, brush heights are consistently at a minimum in the melt, indicative of chains collapsed on the particle surface. The conformational extremes for grafted bottlebrush polymers are unseen in any linear polymer chain systems, highlighting the effect of macromolecular architecture and surface grafting. Bottlebrush grafted particles are an exciting class of materials where diversifying polymer architectures will expand PGP material design rules that harness macromolecular architecture to dictate properties.