Abstract
AbstractFor some genes, notably essential genes, expression when expression is needed is vital hence low noise in expression is favourable. For others noise is necessary for coping with stochasticity or for providing dice-like mechanisms to control cell fate. But how is noise in gene expression modulated? We hypothesise that gene orientation may be crucial, as for divergently organized gene pairs expression of one gene could affect chromatin of a neighbour thereby reducing noise. Transcription of antisense non-coding RNA from a shared promoter is similarly argued to be a noise-reduction mechanism. Stochastic simulation models confirm the expectation. The model correctly predicts: that protein coding genes with bi-promoter architecture, including those with a ncRNA partner, have lower noise than other genes; divergent gene pairs uniquely have correlated expression noise; distance between promoters predicts noise; ncRNA divergent transcripts are associated with genes that a priori would be under selection for low noise; essential genes reside in divergent orientation more than expected; bi-promoter pairs are rare subtelomerically, cluster together and are enriched in essential gene clusters. We conclude that gene orientation and transcription of ncRNAs, even if unstable, are candidate modulators of noise levels.
Highlights
Between genetically identical cells we see variation in abundance of any given transcript or protein
Is low noise a general property of genes associated with ncRNAs, regardless of orientation, or is the divergent orientation important? We find that noise levels of proteins with an ncRNA from the same strand as the protein coding gene have higher expression noise than proteins with a ncRNA derived from a bidirectional promoter
We take three transcription factors that each regulate more than 100 genes and ask whether the mean expression noise of bi-promoter genes bound by these three TFs is lower than the noise of other genes that are bound by the same TFs
Summary
Between genetically identical cells we see variation in abundance of any given transcript or protein. For the chromatin to remain open and for noise to be reduced, permitting expression when expression is needed, polII priming or transcription of a ncRNA through a promoter on the opposite strand to that of the focal protein coding gene would be an efficient mechanism to enable accessibility of the promoter domain of the focal gene.
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