An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors
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| Názov: | An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors |
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| Autori: | Susanne Mandrup, Ville Paakinaho, Diana A. Stavreva, Thomas A. Johnson, Lorenzo Rinaldi, David A. Garcia, Gordon L. Hager, Diego M. Presman, Grégory Fettweis, Kaustubh Wagh, Arpita Upadhyaya, Rikke A.M. Jensen |
| Zdroj: | Garcia, D A, Johnson, T A, Presman, D M, Fettweis, G, Wagh, K, Rinaldi, L, Stavreva, D A, Paakinaho, V, Jensen, R A M, Mandrup, S, Upadhyaya, A & Hager, G L 2021, ' An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors ', Molecular Cell, vol. 81, no. 7, pp. 1484-1498 . https://doi.org/10.1016/j.molcel.2021.01.013 |
| Informácie o vydavateľovi: | Elsevier BV, 2021. |
| Rok vydania: | 2021 |
| Predmety: | 0301 basic medicine, intrinsically disordered regions, GRMON, Transcription Factors/genetics, GRDIM, CONFINEMENT, Receptors, Glucocorticoid/chemistry, Biochimie, biophysique & biologie moléculaire, PPAR, Mice, 03 medical and health sciences, Receptors, Glucocorticoid, glucocorticoid receptor, Receptors, Glucocorticoid/genetics, BI-EXPONENTIAL, Animals, POWER-LAW, Transcription Factors/metabolism, SINGLE-MOLECULE, Molecular Biology, Receptors, Glucocorticoid/metabolism, 0303 health sciences, CHROMATIN BINDING, GRmon, Intrinsically Disordered Proteins/metabolism, GRdim, chromatin binding, Cell Biology, Transcription Factors/chemistry, TRANSCRIPTION DYNAMICS, Life sciences, Rats, Intrinsically Disordered Proteins, Intrinsically Disordered Proteins/chemistry, power-law, confinement, GLUCOCORTICOID RECEPTOR, Sciences du vivant, Intrinsically Disordered Proteins/genetics, INTRINSICALLY DISORDERED REGIONS, Female, single-molecule, transcription dynamics, bi-exponential, Biochemistry, biophysics & molecular biology, Transcription Factors |
| Popis: | Transcription factors (TFs) regulate gene expression by binding to specific consensus motifs within the local chromatin context. The mechanisms by which TFs navigate the nuclear environment as they search for binding sites remain unclear. Here, we used single-molecule tracking and machine-learning-based classification to directly measure the nuclear mobility of the glucocorticoid receptor (GR) in live cells. We revealed two distinct and dynamic low-mobility populations. One accounts for specific binding to chromatin, while the other represents a confinement state that requires an intrinsically disordered region (IDR), implicated in liquid-liquid condensate subdomains. Further analysis showed that the dwell times of both subpopulations follow a power-law distribution, consistent with a broad distribution of affinities on the GR cistrome and interactome. Together, our data link IDRs with a confinement state that is functionally distinct from specific chromatin binding and modulates the transcriptional output by increasing the local concentration of TFs at specific sites. |
| Druh dokumentu: | Article |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2021.01.013 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/33561389 https://pubmed.ncbi.nlm.nih.gov/33561389/ https://www.ncbi.nlm.nih.gov/pubmed/33561389 https://www.sciencedirect.com/science/article/pii/S1097276521000137 http://europepmc.org/article/MED/33561389 https://portal.findresearcher.sdu.dk/da/publications/an-intrinsically-disordered-region-mediated-confinement-state-con http://www.ncbi.nlm.nih.gov/pubmed/33561389 https://hdl.handle.net/2268/303031 https://doi.org/10.1016/j.molcel.2021.01.013 https://portal.findresearcher.sdu.dk/da/publications/fd6e8ddf-9c32-4533-bf0c-0734c797c6cd https://doi.org/10.1016/j.molcel.2021.01.013 https://portal.findresearcher.sdu.dk/da/publications/fd6e8ddf-9c32-4533-bf0c-0734c797c6cd http://hdl.handle.net/11336/175283 |
| Rights: | Elsevier Non-Commercial CC BY NC SA |
| Prístupové číslo: | edsair.doi.dedup.....f161faca86b8e81444c1c50149dedf49 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Transcription factors (TFs) regulate gene expression by binding to specific consensus motifs within the local chromatin context. The mechanisms by which TFs navigate the nuclear environment as they search for binding sites remain unclear. Here, we used single-molecule tracking and machine-learning-based classification to directly measure the nuclear mobility of the glucocorticoid receptor (GR) in live cells. We revealed two distinct and dynamic low-mobility populations. One accounts for specific binding to chromatin, while the other represents a confinement state that requires an intrinsically disordered region (IDR), implicated in liquid-liquid condensate subdomains. Further analysis showed that the dwell times of both subpopulations follow a power-law distribution, consistent with a broad distribution of affinities on the GR cistrome and interactome. Together, our data link IDRs with a confinement state that is functionally distinct from specific chromatin binding and modulates the transcriptional output by increasing the local concentration of TFs at specific sites. |
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| ISSN: | 10972765 |
| DOI: | 10.1016/j.molcel.2021.01.013 |