A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas.
Certain human DNA regions are strikingly undermethylated at CpG sites in sperm 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 status of which changes during spermatogenesis, embryonal growth and differentiation. 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 binding column, indicating that it was normally highly methylated. We investigated the methylation status of this sequence. In the normal genome the sequence was methylated, but in the human hepatocellular carcinoma (HCC) genome, the target sequence was demethylated at the cytosine residue of the CpG dinucleotides with high frequency (75% in the previous study). These data suggest that this regional DNA hypomethylation may play a role in both cell differentiation and hepatocarcinogenesis.
Nagai
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kim
Y S
YS
Yasuda
T
T
Ohmachi
Y
Y
Yokouchi
H
H
Monden
M
M
Emi
M
M
Konishi
N
N
Nogami
M
M
Okumura
K
K
Matsubara
K
K
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002417:Cattle; D002645:Chickens; D003001:Cloning, Molecular; D018899:CpG Islands; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D006801:Humans; D008099:Liver / Q000502:physiology; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics; D009928:Organ Specificity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping / Q000379:methods; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013094:Spermatozoa / Q000502:physiology*
D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases