BACKGROUND: CpG islands and nucleosome-free regions are both found in promoters. 
However, their association has never been studied. On the other hand, DNA 
methylation is absent in promoters but is enriched in gene bodies. Intragenic 
nucleosomes and their modifications have been recently associated with RNA 
splicing. Because the function of intragenic DNA methylation remains unclear, I 
explored the possibility of its involvement in splicing regulation.
RESULTS: 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.
CONCLUSIONS: 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.