Chromatin arranges in filaments of blobs with nanoscale functional zonation, bioRxiv, 2019-03-05

Three-dimensional (3D) chromatin organisation plays a key role in regulating genome function in higher eukaryotes. Despite recognition that the genome partitions into ~1Mb-sized topological associated domains (TADs) based on ensemble Hi-C measurements, many features of the physical organisation at the single cell level remain underexplored. Using 3D super-resolution microscopy, we reveal a sequential curvilinear arrangement of globular chromatin domains with viscoelastic properties (‘blobs’) juxtaposed to an RNA-populated interchromatin (IC) network. Quantitative mapping of genome function markers uncovers a zonal distribution, with RNA-binding factors concentrated in the IC, confinement of structural proteins and transcriptionally activepermissive marks to chromatin domain surfaces, and enrichment of repressive marks towards the interior. This correlation between nanoscale topology and genome function is relaxed in postreplicative chromatin, accentuated in replicative senescence, persists upon ATP depletion and hyperosmolarity induced chromatin condensation and, remarkably, after inactivation of cohesin. Our findings support a model of a higher-order chromatin architecture on the size level of TADs that creates and modulates distinct functional environments through a combination of biophysical parameters such as density and ATP-driven processes such as replication and transcription, but independent of cohesin.

biorxiv genomics 0-100-users 2019

 

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