A novel sperm-specific hypomethylation sequence is a demethylation hotspotin human hepatocellular carcinomas

Certain human DNA regions are strikingly undermethylated at CpG sites in sp erm compared to adult somatic tissues. These sperm-specific hypomethylation sequences are thought to function early in embryogenesis or gametogenesis. By using the restriction landmark genomic scanning (RLGS) cloning method, we have isolated a novel sperm-specific hypomethylation sequence, the statu s of which changes during spermatogenesis, embryonal growth and differentia tion. This sequence is a part of a new 'NotI repeat' consisting of a 1.4 kb repetitive unit sequence named DE-1. The sequence is GC-rich and has high homology to a CpG DNA clone that was isolated by a methyl CpG protein bindi ng column, indicating that it was normally highly methylated. We investigat ed the methylation status of this sequence. In the normal genome the sequen ce was methylated, but in the human hepatocellular carcinoma (HCC) genome, the target sequence was demethylated at the cytosine residue of the CpG din ucleotides with high frequency (75% in the previous study). These data sugg est that this regional DNA hypomethylation may play a role in both cell dif ferentiation and hepatocarcinogenesis. (C) 1999 Elsevier Science B.V. All r ights reserved.