Abstract
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 alpha (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.
