Isolation of CpG Islands From BAC Clones Using a Methyl-CpG Binding Column

Vertebrate genomes are globally heavily methylated at the sequence CpG with the exception of short patches of GC-rich DNA, usually between 1–2 kb in size, which are free of methylation and these are known as CpG islands (see refs. 1 and 2 for reviews). In addition to distinctive DNA characteristics, CpG islands have an open chromatin structure in that they are hyperacetylated, lack histone H1, and have a nucleosome-free region (3 ). The major reason for interest in CpG islands is that they colocalize with the 5′ end of genes. Both promoter sequences and the 5′ parts of transcription units are found within CpG islands. It has been estimated that 56% of human genes and 47% of mouse genes are associated with a CpG island (4 ) and these include all ubiquitously expressed genes as well as many genes with a tissue-restricted pattern of expression (5 ,6 ). Before the draft human sequence became available the number of CpG islands in the human genome was estimated to be 34,200 (4 as modified by 7) and this figure is reasonably close to the 28,890 potential CpG islands that have been identified so far in the draft human genomic sequence (8 ).