Chromatin arranges in filaments of blobs with nanoscale functional zonation

Miron, E.; Oldenkamp, R.; Pinto, D. M.; Brown, J. M.; Carvalho Faria, A. R.; Shaban, H. A.; Rhodes, J. D.; Innocent, C.; de Ornellas, S.; Buckle, V.; Schermelleh, L.

doi:10.1101/566638

bioRxiv · 10.1101/566638

Chromatin arranges in filaments of blobs with nanoscale functional zonation

Miron, E.·Oldenkamp, R.·Pinto, D. M.·Brown, J. M.·Carvalho Faria, A. R.·Shaban, H. A.·Rhodes, J. D.·Innocent, C.·de Ornellas, S.·Buckle, V.·Schermelleh, L.

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Abstract

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 post-replicative chromatin, but remarkably persists after ablation of cohesin. Our findings establish CDs as physical and functional modules of mesoscale genome organization.

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Miron, E., Oldenkamp, R., Pinto, D. M., Brown, J. M., Carvalho Faria, A. R., Shaban, H. A., Rhodes, J. D., Innocent, C., de Ornellas, S., Buckle, V., Schermelleh, L.. 2019-03-04. Chromatin arranges in filaments of blobs with nanoscale functional zonation. https://doi.org/10.1101/566638

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