Indeed, in a study of the HIC1 gene, CpG island methylation inside exon 3 was present in normal controls, which was not associated with down-regulation of HIC1, and hence unimportant for transcriptional regulation of HIC1. In contrast, CpG sites in the 5′UTR was unmethylated in normal marrow control, but aberrantly methylated in some AML samples, thereby emphasizing the importance of methylation of 5′UTR, promoter-associated CpG islands, instead of downstream CpG sites in the translated exonic region in epigenetic regulation of gene expression [35]. This evidence concerns the gene HIC1 and acute myeloid leukemia.