Enhancer Control of Transcriptional Bursting

Cell, Journal Year: 2016, Volume and Issue: 166(2), P. 358 - 368

Published: June 12, 2016

Language: Английский

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Transcription in Living Cells: Molecular Mechanisms of Bursting

Annual Review of Biochemistry, Journal Year: 2020, Volume and Issue: 89(1), P. 189 - 212

Published: March 25, 2020

Transcription in several organisms from certain bacteria to humans has been observed be stochastic nature: toggling between active and inactive states. Periods of nascent RNA synthesis known as bursts represent individual gene activation events which multiple polymerases are initiated. Therefore, bursting is the single locus illustration both repression. Although transcriptional was originally decades ago, only recently have technological advances enabled field begin elucidating regulation at single-locus level. In this review, we focus on how biochemical, genomic, single-cell data describe regulatory steps bursts.

Language: Английский

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What Is a Transcriptional Burst?

Trends in Genetics, Journal Year: 2020, Volume and Issue: 36(4), P. 288 - 297

Published: Feb. 5, 2020

Language: Английский

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A Growing Toolbox to Image Gene Expression in Single Cells: Sensitive Approaches for Demanding Challenges

Molecular Cell, Journal Year: 2018, Volume and Issue: 71(3), P. 468 - 480

Published: Aug. 1, 2018

Language: Английский

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RNA polymerase II speed: a key player in controlling and adapting transcriptome composition

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(15)

Published: July 13, 2021

RNA polymerase II (RNA Pol II) speed or elongation rate, i.e., the number of nucleotides synthesized per unit time, is a major determinant transcriptome composition. It controls co-transcriptional processes such as splicing, polyadenylation, and transcription termination, thus regulating production alternative splice variants, circular RNAs, alternatively polyadenylated transcripts, read-through transcripts. itself regulated in response to intra- extra-cellular stimuli can turn affect composition these stimuli. Evidence points potentially important role modification through regulation for adaptation cells changing environment, pointing function cellular physiology. Analyzing dynamics may therefore be central fully understand physiological processes, development multicellular organisms. Recent findings also raise possibility that deregulation detrimental participate disease progression. Here, we review initial current approaches measure speed, well providing an overview factors controlling which are affected. Finally, discuss cell

Language: Английский

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UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 3, 2022

Abstract The recent breakthrough of single-cell RNA velocity methods brings attractive promises to reveal directed trajectory on cell differentiation, states transition and response perturbations. However, the existing are often found return erroneous results, partly due model violation or lack temporal regularization. Here, we present UniTVelo, a statistical framework that models dynamics spliced unspliced RNAs via flexible transcription activities. Uniquely, it also supports inference unified latent time across transcriptome. With ten datasets, demonstrate UniTVelo returns expected in different biological systems, including hematopoietic differentiation those even with weak kinetics complex branches.

Language: Английский

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Direct observation of a condensate effect on super-enhancer controlled gene bursting

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 331 - 344.e17

Published: Jan. 1, 2024

Enhancers are distal DNA elements believed to loop and contact promoters control gene expression. Recently, we found diffraction-sized transcriptional condensates at genes controlled by clusters of enhancers (super-enhancers). However, a direct function endogenous in controlling expression remains elusive. Here, develop live-cell super-resolution multi-color 3D-imaging approaches investigate putative roles the regulation super-enhancer Sox2. In contrast enhancer distance, find instead that condensate's positional dynamics better predictor A basal bursting occurs when condensate is far (>1 μm), but burst size frequency enhanced moves proximity (<1 μm). Perturbations cohesin local do not prevent affect its enhancement. We propose three-way kissing model whereby interacts transiently with locus regulatory bursting.

Language: Английский

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Time will tell: comparing timescales to gain insight into transcriptional bursting

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(2), P. 160 - 174

Published: Jan. 12, 2024

Recent imaging studies have captured the dynamics of regulatory events transcription inside living cells. These include factor (TF) DNA binding, chromatin remodeling and modification, enhancer-promoter (E-P) proximity, cluster formation, preinitiation complex (PIC) assembly. Together, these molecular culminate in stochastic bursts RNA synthesis, but their kinetic relationship remains largely unclear. In this review, we compare timescales upstream steps (input) with kinetics transcriptional bursting (output) to generate mechanistic models single We highlight open questions potential technical advances guide future endeavors toward a quantitative understanding regulation.

Language: Английский

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An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation

Molecular Cell, Journal Year: 2018, Volume and Issue: 70(4), P. 745 - 756.e6

Published: May 1, 2018

Transcription is a highly regulated and inherently stochastic process. The complexity of signal transduction gene regulation makes it challenging to analyze how the dynamic activity transcriptional regulators affects transcription. By combining fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells an experimental setup for precise spatiotemporal delivery light inputs, we constructed platform real-time, single-cell interrogation Saccharomyces cerevisiae. We show that activation deactivation are fast memoryless. analyzing temporal individual cells, found occurs bursts, whose duration timing modulated by activity. Using our platform, via light-driven feedback loops at level. Feedback markedly reduced cell-to-cell variability led qualitative differences cellular dynamics. Our establishes flexible method studying dynamics single cells.

Language: Английский

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What shapes eukaryotic transcriptional bursting?

Molecular BioSystems, Journal Year: 2017, Volume and Issue: 13(7), P. 1280 - 1290

Published: Jan. 1, 2017

Isogenic cells in a common environment present large degree of heterogeneity gene expression. Part this variability is attributed to transcriptional bursting: the stochastic activation and inactivation promoters that leads discontinuous production mRNA. The diversity bursting patterns displayed by different genes suggests existence connection between regulation. Experimental strategies such as single-molecule RNA FISH, MS2-GFP or short-lived protein reporters allow quantification comparison kinetics conditions, allowing therefore identification molecular mechanisms modulating bursting. In review we recapitulate impact on aspects transcription chromatin environment, nucleosome occupancy, histone modifications, number affinity regulatory elements, DNA looping factor availability. More specifically, examine their role tuning burst size frequency. While some involved marks can affect every aspect bursting, others predominantly influence (e.g. cis-regulatory elements) frequency availability).

Language: Английский

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