Article Cell The Ground State and Evolution of Promoter Region Directionality Graphical Abstract K. lactis, D. hansenii S. cerevisiae > DNA * 15 10 NET-seq 0 NET-seq 10 15 Nucleosomes Changes in trans-acting factors or cis elements Purge by mutation Fortuitous promoter region Intrinsically bidirectional Evolution Retained promoter region Biased towards coding direction Highlights · Promoter region transcription directionality decreases in a foreign environment · Newly evolved promoter regions equally produce transcription in both directions · The ground state of promoter region directionality is bidirectional . DNA sequences and proteins co-evolve to promote directional transcription Authors Yi Jin, Umut Eser, Kevin Struhl, L. Stirling Churchman Correspondence kevin@hms.harvard.edu (K.S.), churchman@genetics.med.harvard. edu (L.S.C.) In Brief Promoter regions are intrinsically bidirectional and are shaped by evolution to bias transcription of coding transcripts, while suppressing non- coding antisense transcription. Jin et al., 2017, Cell 170, 889-898 CrossMark August 24, 2017 @ 2017 Elsevier Inc. http://dx.doi.org/10.1016/j.cell.2017.07.006 CellPress
Article Cell Yi Jin, 1,3 Umut Eser,2,3 Kevin Struhl,1,* and L. Stirling Churchman 2,4,* 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA 2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA 3These authors contributed equally 4Lead Contact *Correspondence: kevin@hms.harvard.edu (K.S.), churchman@genetics.med.harvard.edu (L.S.C.) http://dx.doi.org/10.1016/j.cell.2017.07.006 The Ground State and Evolution of Promoter Region Directionality SUMMARY Eukaryotic promoter regions are frequently diver- gently 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 tran- script mapping in S. cerevisiae strains containing foreign yeast DNA. Promoter regions in foreign envi- ronments lose the directionality they have in their native species. Strikingly, fortuitous promoter re- gions arising in foreign DNA produce equal transcrip- tion in both directions, indicating that divergent tran- scription is a mechanistic feature that does not imply a function for these transcripts. Fortuitous promoter regions arising during evolution promote bidirec- tional 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. INTRODUCTION Eukaryotic promoter regions are nucleosome-depleted regions that contain binding sites for transcriptional activator proteins and core promoters bound by general transcription factors and RNA polymerase II (Pol II) assembled into a preinitiation complex (Burke et al., 1998; Smale, 1997, 2001; Struhl, 1987; Weis and Reinberg, 1992). Activator-binding sites in promoters and en- hancers can function bidirectionally, but the preinitiation com- plex is intrinsically asymmetric and hence promotes transcrip- tion in only one direction. Nevertheless, most eukaryotic promoter regions generate divergent transcripts, many of which are antisense non-coding RNAs that are rapidly degraded by the nuclear exosome (Almada et al., 2013; Core and Lis, 2008; Flynn et al., 2011; Kilchert et al., 2016; Neil et al., 2009; Ntini et al., 2013; Rege et al., 2015; Seila et al., 2008;