Contrasting chromatin organization of CpG islands and exons in the human genome

Here I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters. Nucleosome-free regions were observed only in promoters containing a CpG island. However, the DNA sequences of CpG islands predicted the opposite pattern, implying a limitation of sequence programs for the determination of nucleosome occupancy. In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes. Exon-enrichment of DNA methylation was specifically found in spliced exons and in exons with weak splice sites. The enrichment patterns were less pronounced in initial exons and in non-coding exons, potentially reflecting a lower need for their splicing. I also found that nucleosomes, DNA methylation, and H3K36me3 marked the exons of transcripts with low, medium, and high gene expression levels, respectively.Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels.A CpG island (CGI) is a stretch of DNA in which the frequency of CpGs is higher than that present in other regions [1]. This unique genomic element is found only in vertebrate genomes and is usually present in the promoters of housekeeping genes. CGIs remain typically unmethylated even with many potential target sites for DNA methylation and their aberrant methylation often leads to gene silencing, for example in cancer cells [2].Gene silencing by DNA methylation is accompanied by local changes in the chromatin structure. A more direct mechanism to regulate chromatin structure is the assembly and disassembly of histone-DNA complexes, or nucleosomes. A hallmark of recent whole-genome profiles of nucleosome posi