Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin

Three-dimensional (3D) chromatin organization plays a key role in regulating mammalian genome function, however many of its physical features at the single-cell level remain underexplored. Here we use 3D super-resolution and scanning electron microscopy to analyze structural and functional nuclear organization in somatic cells. We identify linked chromatin domains (CDs) composed of irregular ~200-300-nm-wide aggregates of nucleosomes that can overlap with individual topologically associating domains and are distinct from a surrounding RNA-populated interchromatin region. High-content mapping uncovers confinement of cohesin and active histone modifications to surfaces and enrichment of repressive modifications towards the core of CDs in both hetero- and euchromatic regions. This nanoscale functional topography is temporarily relaxed in postreplicative chromatin, but remarkably persists after ablation of cohesin. Our findings establish CDs as physical and functional modules of mesoscale genome organization.

Miron E, Oldenkamp R, Brown JM, Pinto DMS, Xu CS, Faria AR, Shaban HA, Rhodes JDP, Innocent C, de Ornellas S, Hess HF, Buckle V, Schermelleh L

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