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Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

ABSTRACT: Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes.

SUBMITTER: Dunham LSS

PROVIDER: S-EPMC5747351 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

Dunham Lee S S LSS Momiji Hiroshi H Harper Claire V CV Downton Polly J PJ Hey Kirsty K McNamara Anne A Featherstone Karen K Spiller David G DG Rand David A DA Finkenstädt Bärbel B White Michael R H MRH Davis Julian R E JRE

Cell systems 20171115 6

Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone ...[more]

PMID: 29153839

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Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

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Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

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