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

Roy David 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 journalArticle

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

Fingerprint

Human Genome
trichostatin A
Gene Expression
Fluorescence Microscopy
Tumor Necrosis Factor-alpha
Genome
Genes

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Transcriptional burst frequency and burst size are equally modulated across the human genome. / Dar, Roy David; Razooky, Brandon S.; Singh, Abhyudai; Trimeloni, Thomas V.; McCollum, James M.; Cox, Chris D.; Simpson, Michael L.; Weinberger, Leor S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 43, 23.10.2012, p. 17454-17459.

Research output: Contribution to journalArticle

Dar, Roy David ; Razooky, Brandon S. ; Singh, Abhyudai ; Trimeloni, Thomas V. ; McCollum, James M. ; Cox, Chris D. ; Simpson, Michael L. ; Weinberger, Leor S. / Transcriptional burst frequency and burst size are equally modulated across the human genome. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 43. pp. 17454-17459.
@article{3d3784e5fa514c40bd6b65f7bad241da,
title = "Transcriptional burst frequency and burst size are equally modulated across the human genome",
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.",
keywords = "Automated single-cell imaging, Human immunodeficiency virus, Long terminal repeat promoter, Stochastic noise",
author = "Dar, {Roy David} and Razooky, {Brandon S.} and Abhyudai Singh and Trimeloni, {Thomas V.} and McCollum, {James M.} and Cox, {Chris D.} and Simpson, {Michael L.} and Weinberger, {Leor S.}",
year = "2012",
month = "10",
day = "23",
doi = "10.1073/pnas.1213530109",
language = "English (US)",
volume = "109",
pages = "17454--17459",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "43",

}

TY - JOUR

T1 - Transcriptional burst frequency and burst size are equally modulated across the human genome

AU - Dar, Roy David

AU - Razooky, Brandon S.

AU - Singh, Abhyudai

AU - Trimeloni, Thomas V.

AU - McCollum, James M.

AU - Cox, Chris D.

AU - Simpson, Michael L.

AU - Weinberger, Leor S.

PY - 2012/10/23

Y1 - 2012/10/23

N2 - 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.

AB - 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.

KW - Automated single-cell imaging

KW - Human immunodeficiency virus

KW - Long terminal repeat promoter

KW - Stochastic noise

UR - http://www.scopus.com/inward/record.url?scp=84867914780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867914780&partnerID=8YFLogxK

U2 - 10.1073/pnas.1213530109

DO - 10.1073/pnas.1213530109

M3 - Article

VL - 109

SP - 17454

EP - 17459

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 43

ER -