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

Roy D. Dar, Brandon S. Razooky, Abhyudai Singh, Thomas V. Trimeloni, James M. McCollum, Chris D. Cox, Michael L. Simpson, Leor S. Weinberger

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)17454-17459
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number43
DOIs
StatePublished - Oct 23 2012
Externally publishedYes

Keywords

  • Automated single-cell imaging
  • Human immunodeficiency virus
  • Long terminal repeat promoter
  • Stochastic noise

ASJC Scopus subject areas

  • General

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