Dynamic Analysis of Stochastic Transcription Cycles

Harper, Claire V.; Finkenstädt, Bärbel; Woodcock, Dan J.; Friedrichsen, Sönke; Semprini, Sabrina; Ashall, Louise; Spiller, David G.; Mullins, John J.; Rand, D.A.J.; Davis, John R.; White, Mike

doi:10.1371/journal.pbio.1000607

Cited by 220 publications

(329 citation statements)

References 50 publications

(76 reference statements)

Supporting

Mentioning

307

Contrasting

Unclassified

Order By: Relevance

“…Both synchronized and unsynchronized cells exhibit similar shifts in noise space (SI Appendix, Fig. S3), indicating that transcriptional bursts appear to be common throughout the cell cycle, as reported (25). The UBC and EF1A promoters showed markedly lower CV 2 values than the LTR promoter ( Fig.…”

Section: Resultssupporting

confidence: 68%

Transcriptional burst frequency and burst size are equally modulated across the human genome

Dar

Razooky

Singh

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

464

571

View full text Add to dashboard Cite

Gene expression occurs either as an episodic process, characterized by pulsatile bursts, or as a constitutive process, characterized by a Poisson-like accumulation of gene products. It is not clear which mode of gene expression (constitutive versus bursty) predominates across a genome or how transcriptional dynamics are influenced by genomic position and promoter sequence. Here, we use time-lapse fluorescence microscopy to analyze 8,000 individual human genomic loci and find that at virtually all loci, episodic bursting—as opposed to constitutive expression—is the predominant mode of expression. Quantitative analysis of the expression dynamics at these 8,000 loci indicates that both the frequency and size of the transcriptional bursts varies equally across the human genome, independent of promoter sequence. Strikingly, weaker expression loci modulate burst frequency to increase activity, whereas stronger expression loci modulate burst size to increase activity. Transcriptional activators such as trichostatin A (TSA) and tumor necrosis factor α (TNF) only modulate burst size and frequency along a constrained trend line governed by the promoter. In summary, transcriptional bursting dominates across the human genome, both burst frequency and burst size vary by chromosomal location, and transcriptional activators alter burst frequency and burst size, depending on the expression level of the locus.

show abstract

Section: Resultssupporting

confidence: 68%

Transcriptional burst frequency and burst size are equally modulated across the human genome

Dar

Razooky

Singh

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

464

571

View full text Add to dashboard Cite

show abstract

“…Therefore, intrinsic fluctuations can potentially affect the two alleles of a gene independently (Elowitz et al, 2002;Raj and van Oudenaarden, 2008). The period of inactivity between transcriptional firing has, in some cases, been associated with remodelling of the chromatin (Harper et al, 2011). Indeed, when assessing the transcriptional activation of identical promoters in single cells using two different reporters, the dynamics were shown to be distinct and independent of cell cycle and were proposed to be due to different chromatin configurations.…”

Section: Non-transcriptional Regulation Of Transcription Factor Hetermentioning

confidence: 99%

Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage

2014

View full text Add to dashboard Cite

When pluripotent cells are exposed to a uniform culture environment they routinely display heterogeneous gene expression. Aspects of this heterogeneity, such as Nanog expression, are linked to differences in the propensity of individual cells to either self-renew or commit towards differentiation. Recent findings have provided new insight into the underlying causes of this heterogeneity, which we summarise here using Nanog, a key regulator of pluripotency, as a model gene. We discuss the role of transcription factor heterogeneity in facilitating the intrinsically dynamic and stochastic nature of the pluripotency network, which in turn provides a potential benefit to a population of cells that needs to balance cell fate decisions.

show abstract

“…Changes in cellular transcription activity, but not transcription pulse duration or pulse intensity, have been detected during Dictyostelium development (Chubb et al, 2006). In mammalian cell lines, characterisation of transcriptional 'bursting' has indicated important roles for the levels of transcription factors (Raj et al, 2006), promoter structure (Suter et al, 2011) and chromatin remodelling (Harper et al, 2011) in determining transcriptional activity, indicating that transcription pulses can be potentially altered and are not deterministic. Here, we report, for the first time, the quantitative assessment of transcriptional dynamics in developing fetal tissue and show that transcription patterns change during tissue development.…”

Section: Discussionmentioning

confidence: 99%

Pulsatile patterns of pituitary hormone gene expression change during development

et al. 2011

Self Cite

View full text Add to dashboard Cite

Important questions in biology have emerged recently concerning the timing of transcription in living cells. Studies on clonal cell lines have shown that transcription is often pulsatile and stochastic, with implications for cellular differentiation. Currently, information regarding transcriptional activity at cellular resolution within a physiological context remains limited. To investigate single-cell transcriptional activity in real-time in living tissue we used bioluminescence imaging of pituitary tissue from transgenic rats in which luciferase gene expression is driven by a pituitary hormone gene promoter. We studied fetal and neonatal pituitary tissue to assess whether dynamic patterns of transcription change during tissue development. We show that gene expression in single cells is highly pulsatile at the time endocrine cells first appear but becomes stabilised as the tissue develops in early neonatal life. This stabilised transcription pattern might depend upon tissue architecture or paracrine signalling, as isolated cells, generated from enzymatic dispersion of the tissue, display pulsatile luminescence. Nascent cells in embryonic tissue also showed coordinated transcription activity over short distances further indicating that cellular context is important for transcription activity. Overall, our data show that cells alter their patterns of gene expression according to their context and developmental stage, with important implications for cellular differentiation.

show abstract

Dynamic Analysis of Stochastic Transcription Cycles

Abstract: Cycling of gene expression in individual cells is controlled by dynamic chromatin remodeling.

Cited by 220 publications

References 50 publications

Transcriptional burst frequency and burst size are equally modulated across the human genome

Transcriptional burst frequency and burst size are equally modulated across the human genome

Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage

Pulsatile patterns of pituitary hormone gene expression change during development

Contact Info

Product

Resources

About