Journal
BIOPHYSICAL JOURNAL
Volume 98, Issue 8, Pages L32-L34Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2010.03.001
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Funding
- U.S. Department of Energy
- California HIV/AIDS Research Program [1D08-SD-019]
- Pew Scholars Foundation
- University of California, San Diego, Center for AIDS Research
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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.
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