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

Gladstone Institutes, San Francisco, CA 94158.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2012; 109(43):17454-9. DOI: 10.1073/pnas.1213530109
Source: PubMed


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.

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Available from: Mike Simpson, Jun 30, 2014
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    • "Recent assays in single cells confirmed transcriptional bursting in many organisms (Golding et al, 2005; Chubb et al, 2006; Raj et al, 2006; Zenklusen et al, 2008). Although not all genes are transcribed in bursts (Zenklusen et al, 2008), bursting appears predominant in mammals (Suter et al, 2011; Dar et al, 2012; Bahar Halpern et al, 2015). The mechanisms causing bursts in eukaryotes are still elusive but most likely involve the interplay between transcription factors (Larson et al, 2013; Senecal et al, 2014), chromatin remodelers (Coulon et al, 2013; Voss & Hager, 2013), the formation of gene loops and pre-initiation complexes (Blake et al, 2003; Zenklusen et al, 2008), and transcription initiation and elongation (Jonkers et al, 2014; Stasevich et al, 2014). "
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