Alternative promoters confer transcriptional robustness
Hjörleifur Einarsson will present work he has been doing as a Ph.D. student with Robin Andersson at the Bioinformatics Centre, Department of Biology, University of Copenhagen.
The correct function of transcriptional regulatory elements and their interplay are fundamental for the precisely coordinated transcriptional activities within a cell. However, genomes are characterized by extensive regulatory variation on a population scale and most genetic events at regulatory elements have no or only weak effects on gene transcriptional output. Invariant gene expression may be secured by transcription factors and redundant enhancers, that provide mutational robustness, thereby preventing phenotypic effects upon genetic or environmental change. It is currently unclear if and how promoter architectures further contribute to such robustness.
Here we use genotype data combined with transcription start site profiling data (CAGE) on total RNA across 81 early Drosophila melanogaster embryos to investigate the effects of individual variation on promoter and gene expression. Using strict criteria, we find that a substantial fraction (10%) of fly eQTL genes are associated with shifts in expression from one promoter to another in response to cis-eQTLs. Interestingly, these promoter switch eQTLs have limited or no effect on the overall gene expression level, demonstrating that certain genes are robust to regulatory genetic variations through promoter switches. We demonstrate the presence of this phenomenon across 109 human lymphoblastoid cell lines, suggesting a conserved mechanism across Metazoa.
Identified promoter switches seem to frequently involve specific core promoter elements and occur within housekeeping genes that are highly and ubiquitously expressed throughout fly development. In contrast, redundant enhancers have mainly been associated with developmental genes.
Our findings suggest a novel mechanism of mutational robustness through permissive alternative promoter gene architectures, which sheds light on the lack of transcriptional and/or phenotypic effects observed for many essential genes.