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Mol Cell. 2012 Oct 12;48(1):5-15. doi: 10.1016/j.molcel.2012.07.003. Epub 2012 Aug 9.

A functional evolutionary approach to identify determinants of nucleosome positioning: a unifying model for establishing the genome-wide pattern.

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Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School,Worcester, MA 01605, USA.


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.

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