Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells.
We have sequenced the promoter region of the murine asparagine synthetase gene and examined its methylation profile in the CpG islands of L-asparaginase-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (prototrophs). In the former, complete methylation of the CpG island is correlated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles, as do cells of the intrinsically asparagine-independent lines L1210 and EL4. A similar phenomenon was seen in normal splenic cells of adult mice. This was age related: no methylation was found in weanlings, but up to 45% of gene copies in animals 18 weeks or older were methylated. It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered.
Peng
H
H
Department of Pathology, North Shore University Hospital, Manhasset, NY 11030, USA.
Shen
N
N
Qian
L
L
Sun
X L
XL
Koduru
P
P
Goodwin
L O
LO
Issa
J P
JP
Broome
J D
JD
D000818:Animals; D001215:Asparaginase / Q000378:metabolism*; D001217:Aspartate-Ammonia Ligase / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D017931:DNA Primers / Q000737:chemistry; D000077209:Decitabine; D005784:Gene Amplification; D008099:Liver / Q000201:enzymology; D008223:Lymphoma / Q000201:enzymology*; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000201:enzymology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017931:DNA Primers; D012333:RNA, Messenger; D000077209:Decitabine; D004247:DNA; D015254:DNA Modification Methylases; D001215:Asparaginase; D001217:Aspartate-Ammonia Ligase; D001374:Azacitidine