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

Abstract

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 structure, low in histone H1 and rich in acetylated histones. We have previously found that the island-like CGCG-rich sites in human DNA are hypersensitive to DNase I upon cloning in Saccharomyces cerevisiae. Here we studied, with a higher resolution, the chromatin formed in yeast by one such site, the CpG island accompanying the human glucose-6-phosphate dehydrogenase gene. We have found two strong hypersensitive sites and several positioned nucleosomes flanking the island despite the absence in yeast of such chromatin fiber-shaping factors as histone H1, methyltransferase, and the tissue-specific transcription factors. This finding, together with similar observations from our laboratories and others supports the idea that variations in GC and/or CpG content substantially contribute to the DNA sequence features modulating the structure of the chromatin. The composition- dependent fluctuations in the accessibility of DNA in the chromatin may constitute an evolutionary advantage and may explain the surprising compositional selection that acts in both the coding and non-coding segments of some genes during mammalian evolution.