A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome

Abstract

Most nucleosomes are well-organized at the 5Ј ends of S. cerevisiae genes where "−1" and "+1" nucleosomes bracket a nucleosome-free promoter region (NFR). How nucleosomal organization is specified by the genome is less clear. Here we establish and inter-relate rules governing genomic nucleosome organization by sequencing DNA from more than one million immunopurified S. cerevisiae nucleosomes (displayed at http://atlas.bx.psu.edu/). Evidence is presented that the organization of nucleosomes throughout genes is largely a consequence of statistical packing principles. The genomic sequence specifies the location of the −1 and +1 nucleosomes. The +1 nucleosome forms a barrier against which nucleosomes are packed, resulting in uniform positioning, which decays at farther distances from the barrier. We present evidence for a novel 3Ј NFR that is present at >95% of all genes. 3Ј NFRs may be important for transcription termination and anti-sense initiation. We present a high-resolution genome-wide map of TFIIB locations that implicates 3Ј NFRs in gene looping.

Chromatin-dependent Transcription Factor Accessibility Rather than Nucleosome Remodeling Predominates during Global Transcriptional Restructuring in Saccharomyces cerevisiae

“…Similar to previous work (Lee et al, 2007), we found that clustering the promoter nucleosome occupancy profiles into more than four groups did not significantly alter our results (data not shown). Our analysis revealed features evident in previous studies of genome-wide nucleosome occupancy (Yuan et al, 2005;Lee et al, 2007;Mavrich et al, 2008;Shivaswamy et al, 2008). Most genes contain 1) a nucleosome-depleted region (NDR) of roughly 200 base pairs in their promoters; 2) a strongly positioned ϩ1 nucleosome, which anchors an array of nucleosomes extending into the ORF; 3) a well positioned Ϫ1 nucleosome; 4) a nucleosome-depleted region at the 3Ј end of the transcript (Supplemental Figure S8); and 5) a deeper NDR in the promoters of highly expressed genes than in those of poorly expressed genes (Supplemental Figure S9).…”

“…Certain genomic regions, such as the middle of longer open reading frames (ORFs), tend to yield hybridization patterns inconsistent with precisely positioned nucleosomes but rather present a pattern interpreted to indicate that different cells in the population contain nucleosomes at different positions (Mavrich et al, 2008). Unlike previously described HMMs, which account for these regions by invoking a "delocalized nucleosome state" of indefinite length (Yuan et al, 2005;Lee et al, 2007), our HMM deconstructs regions of delocalized nucleosomes as multiple overlapping arrays of nucleosomes with partial occurrence in the population.…”

“…Recent genome-wide studies of nucleosome positioning found that most yeast promoters contain an extended nucleosome-depleted region (NDR) that is enriched for transcription factor binding sites (Lee et al, 2004;Yuan et al, 2005;Lee et al, 2007;Mavrich et al, 2008;Shivaswamy et al, 2008). Moreover, sequences to which a transcription factor can bind are often more prevalent in the genome than the sites to which that factor is actually bound in vivo.…”

“…To assess whether this dichotomy applies to most yeast promoters and, if so, which yeast promoters fall into each category, we have explored the positions of nucleosomes across the entire yeast genome under conditions in which a majority of yeast genes undergo significant change in gene expression. Several recent studies have reported the precise nucleosome positions across the yeast genome (Yuan et al, 2005;Lee et al, 2007;Mavrich et al, 2008;Shivaswamy et al, 2008;Kaplan et al, 2009). Most studies of genome-wide nucleosome positioning have been conducted at steady states by using cells grown in rich media.…”

Prediction of Nucleosome Positioning Based on Support Vector Machine

“…3. In fact, the four models show only a modest predictive power with maximal AUC values of 0.57 (Segal [10]), 0.59 (Yuan [11]), 0.64 (Mavrich [12]) and 0.66 (Lee [4]). This suggests that these models scores per se are a poor predictor of nucleosome positions.…”