Imaging dynamic and selective low-complexity domain interactions that control gene transcription
Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-07-27
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Biochemistry, Molecular Biology, Online Only
|
| Published by: |
| _version_ | 1836399016175206400 |
|---|---|
| autor | Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. |
| beschreibung | Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease. |
| citation_standardnr | 6310324 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-07-27 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/361/6400/eaar2555?rss=1 |
| schlagwort | Biochemistry, Molecular Biology, Online Only |
| search_space | articles |
| shingle_author_1 | Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. |
| shingle_author_2 | Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. |
| shingle_author_3 | Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. |
| shingle_author_4 | Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. |
| shingle_catch_all_1 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription Biochemistry, Molecular Biology, Online Only Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease. Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription Biochemistry, Molecular Biology, Online Only Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease. Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription Biochemistry, Molecular Biology, Online Only Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease. Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription Biochemistry, Molecular Biology, Online Only Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease. Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., Tjian, R. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| shingle_title_2 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| shingle_title_3 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| shingle_title_4 | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| timestamp | 2025-06-30T23:36:16.360Z |
| titel | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| titel_suche | Imaging dynamic and selective low-complexity domain interactions that control gene transcription |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6310324 |