title: Influence of Rotational Nucleosome Positioning on Transcription Start Site Selection in Animal Promoters.
abstract: The recruitment of RNA-Pol-II to the transcription start site (TSS) is an important step in gene regulation in all organisms. Core promoter elements (CPE) are conserved sequence motifs that guide Pol-II to the TSS by interacting with specific transcription factors (TFs). However, only a minority of animal promoters contains CPEs. It is still unknown how Pol-II selects the TSS in their absence. Here we present a comparative analysis of promoters' sequence composition and chromatin architecture in five eukaryotic model organisms, which shows the presence of common and unique DNA-encoded features used to organize chromatin. Analysis of Pol-II initiation patterns uncovers that, in the absence of certain CPEs, there is a strong correlation between the spread of initiation and the intensity of the 10 bp periodic signal in the nearest downstream nucleosome. Moreover, promoters' primary and secondary initiation sites show a characteristic 10 bp periodicity in the absence of CPEs. We also show that DNA natural variants in the region immediately downstream the TSS are able to affect both the nucleosome-DNA affinity and Pol-II initiation pattern. These findings support the notion that, in addition to CPEs mediated selection, sequence-induced nucleosome positioning could be a common and conserved mechanism of TSS selection in animals.
authors.affiliation: Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
authors.forename: René
authors.identifier: http://orcid.org/0000-0002-0816-7775
authors.initials: R
authors.lastname: Dreos
authors.affiliation: Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ambrosini
authors.affiliation: Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Bucher
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics*; D024363:Transcription Initiation Site / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D009707:Nucleosomes; D004247:DNA; D012319:RNA Polymerase II