Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression.
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.
Singh
Abhyudai
A
Razooky
Brandon
B
Cox
Chris D
CD
Simpson
Michael L
ML
Weinberger
Leor S
LS
D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013269:Stochastic Processes; D014158:Transcription, Genetic
D049452:Green Fluorescent Proteins
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