lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensat...
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| Այլ հեղինակներ: | |
| Ձևաչափ: | Հոդված |
| Լեզու: | English |
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Springer Science and Business Media LLC
2021
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| Առցանց հասանելիություն: | https://hdl.handle.net/1721.1/134367 |
| _version_ | 1826214428792586240 |
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| author | Daneshvar, Kaveh Ardehali, M Behfar Klein, Isaac A Hsieh, Fu-Kai Kratkiewicz, Arcadia J Mahpour, Amin Cancelliere, Sabrina OL Zhou, Chan Cook, Brett M Li, Wenyang Pondick, Joshua V Gupta, Sweta K Moran, Sean P Young, Richard A Kingston, Robert E Mullen, Alan C |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Daneshvar, Kaveh Ardehali, M Behfar Klein, Isaac A Hsieh, Fu-Kai Kratkiewicz, Arcadia J Mahpour, Amin Cancelliere, Sabrina OL Zhou, Chan Cook, Brett M Li, Wenyang Pondick, Joshua V Gupta, Sweta K Moran, Sean P Young, Richard A Kingston, Robert E Mullen, Alan C |
| author_sort | Daneshvar, Kaveh |
| collection | MIT |
| description | © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein–lncRNA phase-separated condensates have a broader role as regulators of transcription. |
| first_indexed | 2024-09-23T16:05:11Z |
| format | Article |
| id | mit-1721.1/134367 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:05:11Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1343672023-02-17T20:49:36Z lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation Daneshvar, Kaveh Ardehali, M Behfar Klein, Isaac A Hsieh, Fu-Kai Kratkiewicz, Arcadia J Mahpour, Amin Cancelliere, Sabrina OL Zhou, Chan Cook, Brett M Li, Wenyang Pondick, Joshua V Gupta, Sweta K Moran, Sean P Young, Richard A Kingston, Robert E Mullen, Alan C Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein–lncRNA phase-separated condensates have a broader role as regulators of transcription. 2021-10-27T20:04:38Z 2021-10-27T20:04:38Z 2020 2021-08-04T18:25:38Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134367 en 10.1038/S41556-020-0572-2 Nature Cell Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Daneshvar, Kaveh Ardehali, M Behfar Klein, Isaac A Hsieh, Fu-Kai Kratkiewicz, Arcadia J Mahpour, Amin Cancelliere, Sabrina OL Zhou, Chan Cook, Brett M Li, Wenyang Pondick, Joshua V Gupta, Sweta K Moran, Sean P Young, Richard A Kingston, Robert E Mullen, Alan C lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title | lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title_full | lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title_fullStr | lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title_full_unstemmed | lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title_short | lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation |
| title_sort | lncrna digit and brd3 protein form phase separated condensates to regulate endoderm differentiation |
| url | https://hdl.handle.net/1721.1/134367 |
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