Nuclease-hypersensitive chromatin formed by a CpG island in human DNA cloned as an artificial chromosome in yeast

CPG islands are mostly unmethylated GC-, and CpG-rich chromosomal segments overlapping promoter sequences in all housekeeping and many tissue-specific genes in vertebrates. Typically, these islands show an open chromatin stru cture, low in histone H1 and rich in acetylated histones. We have previousl y found that the island-like CGCG-rich sites in human DNA are hypersensitiv e to DNase I upon cloning in Saccharomyces cerevisiae. Here we studied, wit h a higher resolution, the chromatin formed in yeast by one such site, the CpG island accompanying the human glucose-6-phosphate dehydrogenase gene. W e have found two strong hypersensitive sites and several positioned nucleos omes flanking the island despite the absence in yeast of such chromatin fib er-shaping factors as histone H1, methyltransferase, and the tissue-specifi c transcription factors. This finding, together with similar observations f rom our laboratories and others supports the idea that variations in GC and /or CpG content substantially contribute to the DNA sequence features modul ating the structure of the chromatin, The composition-dependent fluctuation s in the accessibility of DNA in the chromatin may constitute an, evolution ary advantage and may explain the surprising compositional selection that a cts in both the coding and non-coding segments of some genes during mammali an evolution.