Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding
© 2020 Elsevier Inc. Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains (TADs) is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventio...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/133518 |
| _version_ | 1826196724258963456 |
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| author | Hsieh, Tsung-Han S Cattoglio, Claudia Slobodyanyuk, Elena Hansen, Anders S Rando, Oliver J Tjian, Robert Darzacq, Xavier |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Hsieh, Tsung-Han S Cattoglio, Claudia Slobodyanyuk, Elena Hansen, Anders S Rando, Oliver J Tjian, Robert Darzacq, Xavier |
| author_sort | Hsieh, Tsung-Han S |
| collection | MIT |
| description | © 2020 Elsevier Inc. Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains (TADs) is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventional 3C-based methods by using high-resolution Micro-C to probe links between 3D genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregates TAD regions into various finer-scale structures with distinct regulatory features including stripes, dots, and domains linking promoters-to-promoters (P-P) or enhancers-to-promoters (E-P) and bundle contacts between Polycomb regions. E-P stripes extending from the edge of domains predominantly link co-expressed loci, often in the absence of CTCF and cohesin occupancy. Acute inhibition of transcription disrupts these gene-related folding features without altering higher-order chromatin structures. Our study uncovers previously obscured finer-scale genome organization, establishing functional links between chromatin folding and gene regulation. |
| first_indexed | 2024-09-23T10:36:54Z |
| format | Article |
| id | mit-1721.1/133518 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:36:54Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1335182023-07-28T19:52:08Z Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding Hsieh, Tsung-Han S Cattoglio, Claudia Slobodyanyuk, Elena Hansen, Anders S Rando, Oliver J Tjian, Robert Darzacq, Xavier Massachusetts Institute of Technology. Department of Biological Engineering © 2020 Elsevier Inc. Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains (TADs) is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventional 3C-based methods by using high-resolution Micro-C to probe links between 3D genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregates TAD regions into various finer-scale structures with distinct regulatory features including stripes, dots, and domains linking promoters-to-promoters (P-P) or enhancers-to-promoters (E-P) and bundle contacts between Polycomb regions. E-P stripes extending from the edge of domains predominantly link co-expressed loci, often in the absence of CTCF and cohesin occupancy. Acute inhibition of transcription disrupts these gene-related folding features without altering higher-order chromatin structures. Our study uncovers previously obscured finer-scale genome organization, establishing functional links between chromatin folding and gene regulation. 2021-10-27T19:53:18Z 2021-10-27T19:53:18Z 2020 2021-08-27T18:23:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133518 en 10.1016/J.MOLCEL.2020.03.002 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Hsieh, Tsung-Han S Cattoglio, Claudia Slobodyanyuk, Elena Hansen, Anders S Rando, Oliver J Tjian, Robert Darzacq, Xavier Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title | Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title_full | Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title_fullStr | Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title_full_unstemmed | Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title_short | Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding |
| title_sort | resolving the 3d landscape of transcription linked mammalian chromatin folding |
| url | https://hdl.handle.net/1721.1/133518 |
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