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1.
Exp Mol Med ; 56(4): 820-826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658705

RESUMO

Eukaryotic transcription, a fundamental process that governs cell-specific gene expression, has long been the subject of extensive investigations in the fields of molecular biology, biochemistry, and structural biology. Recent advances in microscopy techniques have led to a fascinating concept known as "transcriptional condensates." These dynamic assemblies are the result of a phenomenon called liquid‒liquid phase separation, which is driven by multivalent interactions between the constituent proteins in cells. The essential proteins associated with transcription are concentrated in transcriptional condensates. Recent studies have shed light on the temporal dynamics of transcriptional condensates and their potential role in enhancing the efficiency of transcription. In this article, we explore the properties of transcriptional condensates, investigate how they evolve over time, and evaluate the significant impact they have on the process of transcription. Furthermore, we highlight innovative techniques that allow us to manipulate these condensates, thus demonstrating their responsiveness to cellular signals and their connection to transcriptional bursting. As our understanding of transcriptional condensates continues to grow, they are poised to revolutionize our understanding of eukaryotic gene regulation.


Assuntos
Transcrição Gênica , Humanos , Animais , Regulação da Expressão Gênica , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/química
2.
Nat Nanotechnol ; 18(3): 257-263, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36702953

RESUMO

Combining highly coherent spin control with efficient light-matter coupling offers great opportunities for quantum communication and computing. Optically active semiconductor quantum dots have unparalleled photonic properties but also modest spin coherence limited by their resident nuclei. The nuclear inhomogeneity has thus far bound all dynamical decoupling measurements to a few microseconds. Here, we eliminate this inhomogeneity using lattice-matched GaAs-AlGaAs quantum dot devices and demonstrate dynamical decoupling of the electron spin qubit beyond 0.113(3) ms. Leveraging the 99.30(5)% visibility of our optical π-pulse gates, we use up to Nπ = 81 decoupling pulses and find a coherence time scaling of [Formula: see text]. This scaling manifests an ideal refocusing of strong interactions between the electron and the nuclear spin ensemble, free of extrinsic noise, which holds the promise of lifetime-limited spin coherence. Our findings demonstrate that the most punishing material science challenge for such quantum dot devices has a remedy and constitute the basis for highly coherent spin-photon interfaces.

3.
Front Cell Dev Biol ; 10: 822026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874812

RESUMO

Recent studies with single-particle tracking in live cells have revealed that chromatin dynamics are directly affected by transcription. However, how transcription alters the chromatin movements followed by changes in the physical properties of chromatin has not been elucidated. Here, we measured diffusion characteristics of chromatin by targeting telomeric DNA repeats with CRISPR-labeling. We found that transcription inhibitors that directly block transcription factors globally increased the movements of chromatin, while the other inhibitor that blocks transcription by DNA intercalating showed an opposite effect. We hypothesized that the increased mobility of chromatin by transcription inhibition and the decreased chromatin movement by a DNA intercalating inhibitor is due to alterations in chromatin rigidity. We also tested how volume confinement of nuclear space affects chromatin movements. We observed decreased chromatin movements under osmotic pressure and with overexpressed chromatin architectural proteins that compact chromatin.

4.
Nucleic Acids Res ; 50(1): 207-226, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34931241

RESUMO

CTCF is crucial to the organization of mammalian genomes into loop structures. According to recent studies, the transcription apparatus is compartmentalized and concentrated at super-enhancers to form phase-separated condensates and drive the expression of cell-identity genes. However, it remains unclear whether and how transcriptional condensates are coupled to higher-order chromatin organization. Here, we show that CTCF is essential for RNA polymerase II (Pol II)-mediated chromatin interactions, which occur as hyperconnected spatial clusters at super-enhancers. We also demonstrate that CTCF clustering, unlike Pol II clustering, is independent of liquid-liquid phase-separation and resistant to perturbation of transcription. Interestingly, clusters of Pol II, BRD4, and MED1 were found to dissolve upon CTCF depletion, but were reinstated upon restoration of CTCF, suggesting a potent instructive function for CTCF in the formation of transcriptional condensates. Overall, we provide evidence suggesting that CTCF-mediated chromatin looping acts as an architectural prerequisite for the assembly of phase-separated transcriptional condensates.


Assuntos
Fator de Ligação a CCCTC/metabolismo , Montagem e Desmontagem da Cromatina , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Epigênese Genética , Células HCT116 , Humanos , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/metabolismo , RNA Polimerase II/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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