CpG Island DNA Has a Low Affinity for Nucleosome Formation

CpG islands in vertebrate genomes are associated not only with housekeeping genes but also with some tissue-restricted genes, including those that comprise the alpha-like globin gene clusters of humans and rabbits. The facts that CpG islands are unmethylated in all tissues (even those not expressing the genes) and that they adopt a unique chromatin structure may have influenced the evolution of mechanisms by which alpha-globin genes are regulated to achieve expression in the correct tissues and the proper developmental stage. We have shown that CpG islands from the alpha-globin gene cluster have positive effects on gene expression, which requires integration into chromosomes and hence is likely to be mediated by effects on chromatin. The potential for a DNA sequence to form a nucleosome complex with core histones is influenced by the topology of that DNA molecule in solution. In light of the unique sequence profile of CpG islands, we tested whether CpG island DNA has a different affinity for nucleosome formation than non-CpG island DNA in a competitive nucleosome reconstitution assay. We find that CpG island DNA from the rabbit alpha-globin gene has a relatively low affinity for core histones in this system. This lower affinity was observed regardless of the position of the fragment in the gene or 5' flanking region. The lower affinity for CpG island DNA showed a length dependence, with the relative affinity for histones decreasing for longer DNA fragments of CpG island DNA. The results are consistent with predictions based on the functional effects of CpG islands and emerging rules for sequences that can exclude nucleosomes.