Transcriptional Bursting from the HIV-1 Promoter is a Significant Source of Stochastic Noise in HIV-1 Gene Expression

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Biophysical Journal

DOI:https://doi.org/10.1016/j.bpj.2010.03.001· OSTI ID:977119

Singh, A ^[1]; Razooky, B ^[1]; Cox, Chris D. ^[2]; Simpson, Michael L ^[3]; Weinberger, Leor S. ^[1]

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1. University of California, San Diego
2. University of Tennessee, Knoxville (UTK)
3. ORNL

Analysis of noise in gene expression has proven a powerful approach for analyzing gene regulatory architecture. To probe the regulatory mechanisms controlling expression of HIV-1, we analyze noise in gene-expression from HIV-1 s long terminal repeat (LTR) promoter at different HIV-1 integration sites across the human genome. Flow cytometry analysis of GFP expression from the HIV-1 LTR shows high variability (noise) at each integration site. Notably, the measured noise levels are inconsistent with constitutive gene expression models. Instead, quantification of expression noise indicates that HIV-1 gene expression occurs through randomly timed bursts of activity from the LTR and that each burst generates an average of 2 10 mRNA transcripts before the promoter returns to an inactive state. These data indicate that transcriptional bursting can generate high variability in HIV-1 early gene products, which may critically influence the viral fate-decision between active replication and proviral latency.

• Research Organization: Oak Ridge National Laboratory (ORNL); Center for Nanophase Materials Sciences
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 977119
• Journal Information: Biophysical Journal, Journal Name: Biophysical Journal Journal Issue: 8 Vol. 98; ISSN 0006-3495; ISSN BIOJAU
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ARCHITECTURE
GENES
PROBES
PROMOTERS