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

Journal Article · · Biophysical Journal
 [1];  [1];  [2];  [3];  [1]
  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 Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)
Sponsoring Organization:
USDOE Office of Science (SC)
DOE Contract Number:
DE-AC05-00OR22725
OSTI ID:
977119
Journal Information:
Biophysical Journal, Vol. 98, Issue 8; ISSN 0006-3495
Country of Publication:
United States
Language:
English