p15 CpG island methylation state in normal individuals. Representation of the CpG island of p15 showing CpG site methylation. A schematic of the p15 CpG island is shown at the top for reference, and transcription start is denoted by the arrow. The symbols above the schematic represent potentialtrans-acting factor binding sites. (▴) Sp1 binding sites.34 Sunbursts downstream of transcription start () represent several additional potential Sp1 binding sites. (★) represents a potential G/T box. (◢) represents a purine/pyrimidine tract that binds an unidentified potentialtrans-acting factor on gel shift analysis (data not shown). For each sequenced leukemia, each row represents an individual cloned and sequenced allele following sodium bisulfite DNA modification. CpG sites are marked as circles and drawn to accurately reflect CpG density of the region. (•) Methylated CpG sites; (○) unmethylated sites. “x” represents a CpG site for which sequence data was ambiguous. (A) The p15 CpG island is largely unmethylated in normal lymphocytes taken from 3 individuals. (B) Individual cloned and sequenced alleles from 3 leukemia cell lines: KG1a, Raji, and HL60.