01st June 2020: '3D super-resolution microscopy of chromatin ‘blobs’' - Lothar Schermelleh, MICRON, Oxford, UK
Duration: 1 hour 12 mins
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Abstract:
Three-dimensional (3D) chromatin organisation plays a key role in regulating mammalian genome function. Despite recognition that the genome partitions into ~1Mb-sized topological associated domains (TADs) based on ensemble Hi-C measurements, many of its physical features at the single-cell level remain underexplored. In my talk, I will present our use of super-resolution 3D structured illumination microscopy (3D-SIM) supplemented by focused ion beam scanning electron microscopy (FIB-SEM) to analyse structural and functional nuclear organisation in somatic cells. We identify linked chromatin domains (CDs) composed of irregular ~200-300-nm-wide aggregates of nucleosomes with viscoelastic properties (‘blobs’). These can overlap with individual topologically associating domains (TADs) and are distinct from a surrounding RNA-populated interchromatin region. High-content mapping of functional nuclear marker 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 organisation. Lothar’s research aims at understanding the relationship between 3D nuclear organisation and genome activity in mammalian cells by combining genetic tools and advanced optical imaging methods. Lothar Schemelleh Lothar is an affiliated member of the Micron Advanced Bioimaging Unit (www.micronoxford.com), he is driving the development of computational analysis and fluorescence labelling tools for super-resolution microscopy. His biological research aims at uncovering the interplay between biophysical forces, epigenetic memory and cohesin complex activity to modulate cell-type-specific transcriptional programmes, e.g. during cell differentiation and in pathological states. To this end, his group employs a combination of genetic editing and cell biological manipulations with innovative live-cell and correlative super-resolution imaging and analysis approaches. This will ultimately enable to directly observe genome activity, such as transcription, replication and repair, in the context of the nuclear environment at the nanoscale. Lothar is co-author of super-resolution reviews: A guide to super-resolution fluorescence microscopy. L Schermelleh, R Heintzmann, H Leonhardt, The Journal of Cell Biology 190 (2), 165-175 Super-resolution microscopy demystified. Schermelleh, L., Ferrand, A., Huser, T. et al. Nat Cell Biol 21, 72–84 (2019). https://doi.org/10.1038/s41556-018-0251-8 |
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| Created: | 2020-06-25 16:52 |
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| Collection: | Imaging ONE WORLD |
| Publisher: | University of Cambridge |
| Copyright: | Lothar Schermelleh |
| Language: | eng (English) |
| Distribution: |
World
(not downloadable)
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| Keywords: | super-resolution; chromatin; microscopy; |
| Explicit content: | No |
| Aspect Ratio: | 16:9 |
| Screencast: | No |
| Bumper: | UCS Default |
| Trailer: | UCS Default |
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