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The Ground State and Evolution of Promoter Region Directionality

Jin, Yi, Eser, Umut, Struhl, Kevin, Churchman, L. Stirling
Cell 2017 v.170 pp. 889-898.e10
DNA, DNA-directed RNA polymerase, byproducts, evolution, humans, indigenous species, mutation, non-coding RNA, promoter regions, transcription (genetics), yeasts
Eukaryotic promoter regions are frequently divergently transcribed in vivo, but it is unknown whether the resultant antisense RNAs are a mechanistic by-product of RNA polymerase II (Pol II) transcription or biologically meaningful. Here, we use a functional evolutionary approach that involves nascent transcript mapping in S. cerevisiae strains containing foreign yeast DNA. Promoter regions in foreign environments lose the directionality they have in their native species. Strikingly, fortuitous promoter regions arising in foreign DNA produce equal transcription in both directions, indicating that divergent transcription is a mechanistic feature that does not imply a function for these transcripts. Fortuitous promoter regions arising during evolution promote bidirectional transcription and over time are purged through mutation or retained to enable new functionality. Similarly, human transcription is more bidirectional at newly evolved enhancers and promoter regions. Thus, promoter regions are intrinsically bidirectional and are shaped by evolution to bias transcription toward coding versus non-coding RNAs.