Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation
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Le résumé fourni par la source
CRISPR activation (CRISPRa) is a powerful tool for endogenous gene activation, yet the mechanisms underlying its optimal transcriptional activation remain unclear. By monitoring real-time transcriptional bursts, we find that CRISPRa modulates both burst duration and amplitude. Our quantitative imaging reveals that CRISPR-SunTag activators, with three tandem VP64-p65-Rta (VPR), form liquid-like transcriptional condensates and exhibit high activation potency. Although visible CRISPRa condensates are associated with some RNA bursts, the overall levels of phase separation do not correlate with transcriptional bursting or activation strength in individual cells. When the number of SunTag scaffolds is increased to 10 or more, solid-like condensates form, sequestering co-activators such as p300 and MED1. These condensates display low dynamicity and liquidity, resulting in ineffective gene activation. Overall, our studies characterize various phase-separated CRISPRa systems for gene activation, highlighting the foundational principles for engineering CRISPR-based programmable synthetic condensates with appropriate properties to effectively modulate gene expression. The mechanisms underlying optimal transcriptional activation remain elusive. Here, the authors show that CRISPR-SunTag activators form liquid-like droplets and boost gene expression, while increased SunTag scaffolds creates solid-like condensates that sequester coactivators, impairing activation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation
- Date Crossref
- 14/02/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Zhejiang Chinese Medical University pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Women's Hospital pays non établi dans la noticeÉtablissement de santé
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Guizhou Normal University pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital Zhejiang University pays non établi dans la noticeÉtablissement de santé
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School of Life Science The State Key Laboratory of Southwest Karst Mountain Biodiversity Conservation of Forestry Administration pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang Provincial Key Laboratory of Genetic & Developmental Disorders pays non établi dans la noticeStructure de recherche
Zhejiang Chinese Medical University, Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology — Zhejiang University et Women's Hospital — School of Medicine, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.