Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast

In yeast cells, preferential accessibility of the HIS3-PET56 promoter region is determined by a general property of the DNA sequence, not by defined sequence elements. In vivo, this region is largely devoid of nucleosomes, and accessibility is directly related to reduced histone density. The HIS3-PET56 and DED1 promoter regions associate poorly with histones in vitro, indicating that intrinsic nucleosome stability is a major determinant of preferential accessibility. Specific and genome-wide analyses indicate that low nucleosome density is a very common feature of yeast promoter regions that correlates poorly with transcriptional activation. Thus, the yeast genome is organized into structurally distinct promoter and nonpromoter regions whose DNA sequences inherently differ with respect to nucleosome formation. This organization ensures that transcription factors bind preferentially to appropriate sites in promoters, rather than to the excess of irrelevant sites in nonpromoter regions.