RNA polymerase II clusters form in line with surface condensation on regulatory chromatin
Abstract It is essential for cells to control which genes are transcribed into RNA. In eukaryotes, two major control points are recruitment of RNA polymerase II (Pol II) into a paused state, and subsequent pause release toward transcription. Pol II recruitment and pause release occur in association...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-09-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202110272 |
| _version_ | 1797283357613096960 |
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| author | Agnieszka Pancholi Tim Klingberg Weichun Zhang Roshan Prizak Irina Mamontova Amra Noa Marcel Sobucki Andrei Yu Kobitski Gerd Ulrich Nienhaus Vasily Zaburdaev Lennart Hilbert |
| author_facet | Agnieszka Pancholi Tim Klingberg Weichun Zhang Roshan Prizak Irina Mamontova Amra Noa Marcel Sobucki Andrei Yu Kobitski Gerd Ulrich Nienhaus Vasily Zaburdaev Lennart Hilbert |
| author_sort | Agnieszka Pancholi |
| collection | DOAJ |
| description | Abstract It is essential for cells to control which genes are transcribed into RNA. In eukaryotes, two major control points are recruitment of RNA polymerase II (Pol II) into a paused state, and subsequent pause release toward transcription. Pol II recruitment and pause release occur in association with macromolecular clusters, which were proposed to be formed by a liquid–liquid phase separation mechanism. How such a phase separation mechanism relates to the interaction of Pol II with DNA during recruitment and transcription, however, remains poorly understood. Here, we use live and super‐resolution microscopy in zebrafish embryos to reveal Pol II clusters with a large variety of shapes, which can be explained by a theoretical model in which regulatory chromatin regions provide surfaces for liquid‐phase condensation at concentrations that are too low for canonical liquid–liquid phase separation. Model simulations and chemical perturbation experiments indicate that recruited Pol II contributes to the formation of these surface‐associated condensates, whereas elongating Pol II is excluded from these condensates and thereby drives their unfolding. |
| first_indexed | 2024-03-07T17:30:33Z |
| format | Article |
| id | doaj.art-e2cf57e85b014bc6b986a21ecfb1a26b |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:30:33Z |
| publishDate | 2021-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-e2cf57e85b014bc6b986a21ecfb1a26b2024-03-02T18:07:09ZengSpringer NatureMolecular Systems Biology1744-42922021-09-01179n/an/a10.15252/msb.202110272RNA polymerase II clusters form in line with surface condensation on regulatory chromatinAgnieszka Pancholi0Tim Klingberg1Weichun Zhang2Roshan Prizak3Irina Mamontova4Amra Noa5Marcel Sobucki6Andrei Yu Kobitski7Gerd Ulrich Nienhaus8Vasily Zaburdaev9Lennart Hilbert10Zoological Institute Department of Systems Biology and Bioinformatics Karlsruhe Institute of Technology Karlsruhe GermanyDepartment of Biology Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen GermanyInstitute of Applied Physics Karlsruhe Institute of Technology Karlsruhe GermanyInstitute of Biological and Chemical Systems—Biological Information Processing Karlsruhe Institute of Technology Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems—Biological Information Processing Karlsruhe Institute of Technology Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems—Biological Information Processing Karlsruhe Institute of Technology Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems—Biological Information Processing Karlsruhe Institute of Technology Eggenstein‐Leopoldshafen GermanyInstitute of Applied Physics Karlsruhe Institute of Technology Karlsruhe GermanyInstitute of Biological and Chemical Systems—Biological Information Processing Karlsruhe Institute of Technology Eggenstein‐Leopoldshafen GermanyDepartment of Biology Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen GermanyZoological Institute Department of Systems Biology and Bioinformatics Karlsruhe Institute of Technology Karlsruhe GermanyAbstract It is essential for cells to control which genes are transcribed into RNA. In eukaryotes, two major control points are recruitment of RNA polymerase II (Pol II) into a paused state, and subsequent pause release toward transcription. Pol II recruitment and pause release occur in association with macromolecular clusters, which were proposed to be formed by a liquid–liquid phase separation mechanism. How such a phase separation mechanism relates to the interaction of Pol II with DNA during recruitment and transcription, however, remains poorly understood. Here, we use live and super‐resolution microscopy in zebrafish embryos to reveal Pol II clusters with a large variety of shapes, which can be explained by a theoretical model in which regulatory chromatin regions provide surfaces for liquid‐phase condensation at concentrations that are too low for canonical liquid–liquid phase separation. Model simulations and chemical perturbation experiments indicate that recruited Pol II contributes to the formation of these surface‐associated condensates, whereas elongating Pol II is excluded from these condensates and thereby drives their unfolding.https://doi.org/10.15252/msb.202110272active mattergene regulationnuclear organizationsuper‐resolution microscopytranscriptional condensates |
| spellingShingle | Agnieszka Pancholi Tim Klingberg Weichun Zhang Roshan Prizak Irina Mamontova Amra Noa Marcel Sobucki Andrei Yu Kobitski Gerd Ulrich Nienhaus Vasily Zaburdaev Lennart Hilbert RNA polymerase II clusters form in line with surface condensation on regulatory chromatin Molecular Systems Biology active matter gene regulation nuclear organization super‐resolution microscopy transcriptional condensates |
| title | RNA polymerase II clusters form in line with surface condensation on regulatory chromatin |
| title_full | RNA polymerase II clusters form in line with surface condensation on regulatory chromatin |
| title_fullStr | RNA polymerase II clusters form in line with surface condensation on regulatory chromatin |
| title_full_unstemmed | RNA polymerase II clusters form in line with surface condensation on regulatory chromatin |
| title_short | RNA polymerase II clusters form in line with surface condensation on regulatory chromatin |
| title_sort | rna polymerase ii clusters form in line with surface condensation on regulatory chromatin |
| topic | active matter gene regulation nuclear organization super‐resolution microscopy transcriptional condensates |
| url | https://doi.org/10.15252/msb.202110272 |
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