Figure 3. .

CpG islands in the GGH promoter region. A, Two CpG islands in the GGH 5′ promoter region extend into intron 1. The CpG1 and CpG2 regions (shaded areas) are indicated relative to the A of the translation start codon, defined as nt +1. B, Sequence of the GGH promoter region (nt −905 to −118) of each allele in the Nalm6 cell line and primary leukemia cells from five cases of ALL, determined by bisulfite sequencing. GGH promoter methylation was confirmed by NMSP in all five cases (data not shown). Each box represents a CpG dinucleotide; methylated CpG sites are blackened; unmethylated CpG sites are unblackened. The polymorphisms at nt −649, −249, and −209 were used to define allelic methylation. C, Regulation of transcriptional activity of GGH promoter by selective in vitro methylation of CpG islands in the GGH promoter region. The left panel shows a schematic diagram of the individually methylated CpG islands within GGH promoter constructs linked to a luciferase reporter. Methylated CpG island fragments are blackened; unmethylated fragments are unblackened.