Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes
The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/129491 |
| _version_ | 1811084803847487488 |
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| author | Zamudio Montes de Oca, Alicia Dall’Agnese, Alessandra Henninger, Jonathan E. Manteiga, John Colonnese Afeyan, Lena K. Hannett, Nancy M. Coffey, Eliot Leo Li, Charles Han Oksuz, Ozgur Sabari, Benjamin R. Boija, Ann Klein, Isaac A. Hawken, Susana W Spille, Jan Hendrik Cisse, Ibrahim I Abraham, Brian Joseph Lee, Tong Ihn Taatjes, Dylan J. Schuijers, Jurian Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Zamudio Montes de Oca, Alicia Dall’Agnese, Alessandra Henninger, Jonathan E. Manteiga, John Colonnese Afeyan, Lena K. Hannett, Nancy M. Coffey, Eliot Leo Li, Charles Han Oksuz, Ozgur Sabari, Benjamin R. Boija, Ann Klein, Isaac A. Hawken, Susana W Spille, Jan Hendrik Cisse, Ibrahim I Abraham, Brian Joseph Lee, Tong Ihn Taatjes, Dylan J. Schuijers, Jurian Young, Richard A. |
| author_sort | Zamudio Montes de Oca, Alicia |
| collection | MIT |
| description | The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity. |
| first_indexed | 2024-09-23T12:57:32Z |
| format | Article |
| id | mit-1721.1/129491 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:57:32Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1294912022-09-28T11:10:37Z Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes Zamudio Montes de Oca, Alicia Dall’Agnese, Alessandra Henninger, Jonathan E. Manteiga, John Colonnese Afeyan, Lena K. Hannett, Nancy M. Coffey, Eliot Leo Li, Charles Han Oksuz, Ozgur Sabari, Benjamin R. Boija, Ann Klein, Isaac A. Hawken, Susana W Spille, Jan Hendrik Cisse, Ibrahim I Abraham, Brian Joseph Lee, Tong Ihn Taatjes, Dylan J. Schuijers, Jurian Young, Richard A. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Physics Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Computational and Systems Biology Program The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity. National Science Foundation (U.S.). (Grant PHY1743900) National Institutes of Health (U.S.) (Grants GM123511, GM117370 and T32CA009172) German Research Foundation Research Fellowship (DE 3069/1-1) 2021-01-21T16:43:27Z 2021-01-21T16:43:27Z 2019-12 2020-12-16T16:05:02Z Article http://purl.org/eprint/type/JournalArticle 1097-2765 https://hdl.handle.net/1721.1/129491 Zamudio, Alicia V. et al. “Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes.” Molecular Cell, 76, 5 (December 2019): 753–766.e6 © 2019 The Author(s) en 10.1016/J.MOLCEL.2019.08.016 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Zamudio Montes de Oca, Alicia Dall’Agnese, Alessandra Henninger, Jonathan E. Manteiga, John Colonnese Afeyan, Lena K. Hannett, Nancy M. Coffey, Eliot Leo Li, Charles Han Oksuz, Ozgur Sabari, Benjamin R. Boija, Ann Klein, Isaac A. Hawken, Susana W Spille, Jan Hendrik Cisse, Ibrahim I Abraham, Brian Joseph Lee, Tong Ihn Taatjes, Dylan J. Schuijers, Jurian Young, Richard A. Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title | Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title_full | Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title_fullStr | Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title_full_unstemmed | Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title_short | Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes |
| title_sort | mediator condensates localize signaling factors to key cell identity genes |
| url | https://hdl.handle.net/1721.1/129491 |
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