A Functional Evolutionary Approach to Identify Determinants of Nucleosome Positioning: A Unifying Model for Establishing the Genome-wide Pattern

Although the genomic pattern of nucleosome positioning is broadly conserved, quantitative aspects vary over evolutionary timescales. We identify the cis and trans determinants of nucleosome positioning using a functional evolutionary approach involving S. cerevisiae strains containing large genomic regions from other yeast species. In a foreign species, nucleosome depletion at promoters is maintained over poly(dA:dT) tracts, whereas internucleosome spacing and all other aspects of nucleosome positioning tested are not. Interestingly, the locations of the +1 nucleosome and RNA start sites shift in concert. Strikingly, in a foreign species, nucleosome-depleted regions occur fortuitously in coding regions, and they often act as promoters that are associated with a positioned nucleosome array linked to the length of the transcription unit. We suggest a three-step model in which nucleosome remodelers, general transcription factors, and the transcriptional elongation machinery are primarily involved in generating the nucleosome positioning pattern in vivo. ⺠Systematic dissection of cis and trans contributions to nucleosome positioning ⺠Nucleosome positioning is generally established by proteins, not DNA sequence ⺠Fortuitous promoters establish canonical promoter chromatin architecture ⺠Three-step model for establishment of in vivo nucleosome positioning