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 live- and fixed-cell 3D super-resolution and scanning electron microscopy to analyze structural a...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Association for the Advancement of Science
2020
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| _version_ | 1826293431285055488 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Miron, E |
| collection | OXFORD |
| description | 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 live- and fixed-cell 3D super-resolution and scanning electron microscopy to analyze structural and functional nuclear organization in somatic cells. We identify chains of interlinked ~200- to 300-nm-wide chromatin domains (CDs) composed of aggregated nucleosomes that can overlap with individual topologically associating domains and are distinct from a surrounding RNA-populated interchromatin compartment. High-content mapping uncovers confinement of cohesin and active histone modifications to surfaces and enrichment of repressive modifications toward 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. |
| first_indexed | 2024-03-07T03:30:00Z |
| format | Journal article |
| id | oxford-uuid:ba629888-c52a-4bd2-9610-15e1d3b59569 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:30:00Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:ba629888-c52a-4bd2-9610-15e1d3b595692022-03-27T05:09:37ZChromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba629888-c52a-4bd2-9610-15e1d3b59569EnglishSymplectic ElementsAmerican Association for the Advancement of Science2020Miron, EOldenkamp, RBrown, JMPinto, DMSXu, CSFaria, ARShaban, HARhodes, JDPInnocent, Cde Ornellas, SHess, HFBuckle, VSchermelleh, LThree-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 live- and fixed-cell 3D super-resolution and scanning electron microscopy to analyze structural and functional nuclear organization in somatic cells. We identify chains of interlinked ~200- to 300-nm-wide chromatin domains (CDs) composed of aggregated nucleosomes that can overlap with individual topologically associating domains and are distinct from a surrounding RNA-populated interchromatin compartment. High-content mapping uncovers confinement of cohesin and active histone modifications to surfaces and enrichment of repressive modifications toward 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. |
| spellingShingle | 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 Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title | Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title_full | Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title_fullStr | Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title_full_unstemmed | Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title_short | Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
| title_sort | chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin |
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