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 CpGrich 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.

Divergence of CpG island promoters: A consequence or cause of evolution?

“…The TSS in yeast and worm did not exhibit accumulation of CGIs (Fig. 1a, top panel), which supports the previous observations that CpG islands are absent in their genomes (Mucha et al. 2000; Takai & Jones 2002).…”

“…The TSS in yeast and worm did not exhibit accumulation of CGIs (Fig. 1a, top panel), which supports the previous observations that CpG islands are absent in their genomes (Mucha et al 2000;Takai & Jones 2002). The promoters in fly, however, demonstrated a unique pattern with a general high baseline (background) level (30%), except for the immediate 5¢ proximity of the TSS (10%) (Fig.…”

Non‐random features of loop‐size chromatin fragmentation

“…Interestingly, such patterns of CpG distribution can also be observed in some hot‐spots of BCR rearrangement (not shown). These observations may be related to instances when the GC and/or CpG content of the DNA appeared to influence the propensity for the formation of nuclease hypersensitive regions affecting higher order chromatin organization [Mucha et al, 2000].…”

Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island

“…CpG islands have an alternative structure to bulk chromatin in normal cells (Tazi and Bird, 1990). They are characterized by a lack of cytosine methylation, low levels of histone H1, high levels of histone acetylation, and hypersensitivity to DNaseI which has been equated with nucleosome-free regions (Mucha et al, 2000;Pfeifer and Riggs, 1991;Tazi and Bird, 1990). Genome-wide analysis has shown that DNaseI-sensitive sites are often present in both the expressing and nonexpressing states on many autosomal genes (Mito et al, 2007;Sabo et al, 2004).…”