Abstract
Recent analysis demonstrates that the HIV-1 Long Terminal Repeat (HIV LTR) promoter
exhibits a range of possible transcriptional burst sizes and frequencies for any mean-expression
level. However, these results have also been interpreted as demonstrating that cell-tocell
expression variability (noise) and mean are uncorrelated, a significant deviation from previous
results. Here, we re-examine the available mRNA and protein abundance data for the
HIV LTR and find that noise in mRNA and protein expression scales inversely with the mean
along analytically predicted transcriptional burst-size manifolds. We then experimentally perturb
transcriptional activity to test a prediction of the multiple burst-size model: that increasing
burst frequency will cause mRNA noise to decrease along given burst-size lines as mRNA
levels increase. The data show that mRNA and protein noise decrease as mean expression
increases, supporting the canonical inverse correlation between noise and mean.