A genomic model of condition-specific nucleosome behaviour explains transcriptional activity in yeast

Abstract

Nucleosomes play an important role in gene regulation. Molecular studies observed that nucleosome-binding in promoters tends to be repressive, and that their removal is sufficient to activate transcription. In contrast, genomic studies have delivered conflicting results: an analysis of yeast grown on diverse carbon sources reported that nucleosome-occupancies remain largely unchanged between different conditions; whereas a study of the heat-shock response showed that nucleosomes tend to be evicted from promoters of genes with increased expression. Consequently, there are few general and consistent principles that capture the relationship between chromatin organisation and transcriptional regulation. Here, we present a qualitative model for nucleosome-positioning in the yeast Saccharomyces cerevisiae that helps explain several important properties of gene expression. By integrating publicly available genomic datasets, we observe that promoter-bound nucleosomes assume one of four discrete configurations that determine the active and silent transcriptional states of a gene, but not the actual expression level. In TATA-box-containing promoters, nucleosome architecture indicates the amount of transcriptional noise. By comparing nucleosome-occupancy datasets, we show that over 20% of genes switch promoter states upon changes in cellular conditions, and therefore their transcriptional outputs. The data suggest that a combination of DNA-binding transcription factors and chromatin-remodelling enzymes, rather than the underlying genomic sequence, is primarily responsible for determining the nucleosome architecture. Our model for promoter nucleosome architecture reconciles genome-scale findings with previous molecular studies; in doing so, we establish principles for nucleosome-positioning and gene expression that apply not only to individual genes, but more generally across the entire genome. The study provides a stepping stone for future models of transcriptional regulation that encompass the intricate interplay between cis- and trans-acting factors, chromatin and the core transcriptional machinery.