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

by A Singh, B Razooky, Chris Cox, Michael L Simpson, Leor Weinberger
Publication Type
Journal
Journal Name
Biophysical Journal
Publication Date
Volume
98
Issue
8

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.