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Review
. 2012 Apr 2;13(4):313-21.
doi: 10.1038/embor.2012.31.

Transcription goes digital

Timothée Lionnet  1 , Robert H Singer
Affiliations
Review

Transcription goes digital

Timothée Lionnet et al. EMBO Rep. .

Abstract

Transcription is a complex process that integrates the state of the cell and its environment to generate adequate responses for cell fitness and survival. Recent microscopy experiments have been able to monitor transcription from single genes in individual cells. These observations have revealed two striking features: transcriptional activity can vary markedly from one cell to another, and is subject to large changes over time, sometimes within minutes. How the chromatin structure, transcription machinery assembly and signalling networks generate such patterns is still unclear. In this review, we present the techniques used to investigate transcription from single genes, introduce quantitative modelling tools, and discuss transcription mechanisms and their implications for gene expression regulation.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. Models of transcription bursts.
(A) Left: bursts can appear when fluctuations in the concentration of an upstream factor reach a threshold (grey dashed line), triggering the ‘on’ state of the promoter, allowing transcription to take place. Right: spontaneous bursts occur even when upstream signalling is constant. Red: concentration of an upstream activator. Green: state of the promoter; ‘off’ corresponds to the baseline, ‘on’ corresponds to the high level. Black: each vertical line represents the initiation of the transcription of a single mRNA. (B) Chromatin-based model of bursting: a slow step corresponding to nucleosome dissociation or histone mark deposition triggers the switch from a covered promoter state (off) to an open promoter state (on). In the open state, many sequential initiations are made possible by transient interactions of transcription factors with the promoter.
Figure 2
Figure 2. Relationship between transcriptional noise and promoter architecture in yeast genes.
(A) Plot of the variance compared with mean mRNA copy number for various yeast genes studied by single-molecule FISH reveals two modes of expression: ‘bursty’ (high variance, blue) and constitutive (Poisson-limited variance, red). Housekeeping genes all fall in the constitutive class. All but one cell-cycle-regulated and signal response genes fall in the ‘bursty’ class. Data adapted from Lionnet et al [35]. (B) Promoters of ‘bursty’ genes have a covered architecture (blue), whereas constitutively expressed genes display a pronounced nucleosome-depleted region (red). Data from Lee et al [91], solid line for each class is the average of the genes from panel A, shaded area indicates mean ± s.e.m. TSS, transcription start site.
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Timothée Lionnet & Robert H. Singer
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