Robustness of transcriptional regulatory program influences gene expression variability.
BACKGROUND
Most genes are not affected when any transcription factor (TF) is knocked out, indicating that they have robust transcriptional regulatory program. Yet the mechanism underlying robust transcriptional regulatory program is less clear.


RESULTS
Here, we studied the cause and effect of robust transcriptional regulatory program. We found that cooperative TFs in the robust transcriptional regulatory program regulate their common target genes in an activity-redundant fashion, and they are able to compensate for each other's loss. As a result, their target genes are insensitive to their single perturbation. We next revealed that the degree of robustness of transcriptional regulatory program influences gene expression variability. Genes with fragile (unrobust) transcriptional regulatory program under normal growth condition could be readily reprogrammed to significantly modulate gene expression upon changing conditions. They also have high evolutionary rates of gene expression. We further showed that the fragile transcriptional regulatory program is a major source of expression variability.


CONCLUSIONS
We showed that activity-redundant TFs guarantee the robustness of transcriptional regulatory programs, and the fragility of transcriptional regulatory program plays a major role in gene expression variability. These findings reveal the mechanisms underlying robust transcription and expression variability.
Dai
Zhiming
Z
Electronic Department, Sun Yat-Sen University, Guangzhou, PR China. zhimdai@gmail.com
Dai
Xianhua
X
Xiang
Qian
Q
Feng
Jihua
J
D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic
D014157:Transcription Factors