Premium
5‐methylcytosine is present in the 5′ flanking region of ha‐ ras in mouse liver and increases with ageing
Author(s) -
Counts Jennifer L.,
Kaznowski Janice M.,
McClain R. Michael,
Goodman Jay I.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970729)72:3<491::aid-ijc18>3.0.co;2-f
Subject(s) - methylation , dna methylation , biology , carcinogenesis , cpg site , 5 methylcytosine , epigenetics , gene , microbiology and biotechnology , 5' flanking region , oncogene , mutation , gene expression , genetics , promoter , cell cycle
Modifications to DNA‐5‐methylcytosine (5MeC) content ( i.e., alterations in the level of 5MeC) constitute epigenetic events. In general, hypomethylation of a gene is necessary but not sufficient for expression, while methylated genes typically are quiescent. Ha‐ ras is an oncogene commonly implicated in murine liver tumorigenesis, often, though not always, involving mutation. A PCR‐based approach using pre‐PCR digestion with methylation‐sensitive enzymes was employed to determine the 5MeC content of the 5′ flanking region of this gene in (i) B6C3F 1 and C57BL/6 mouse liver from young animals (4 months old) and (ii) B6C3F 1 mouse liver from aged animals (24 months old). Two segments of the 5′ flanking region of Ha‐ ras were examined. We demonstrate the presence of 5MeC in a portion of the 5′ flanking region of Ha‐ ras that does not share characteristics of a CpG island, while a region that shares CpG island characteristics is primarily unmethylated. Differences in methylation status in these areas of Ha‐ ras were not observed between B6C3F 1 and C57BL/6 mouse livers. Increases in methylation status were observed with ageing in B6C3F 1 mouse liver. These data provide a role for methylation in regulating Ha‐ ras expression in mouse liver. Ha‐ ras in human liver has been reported to be unmethylated. There are substantial sequence differences in a key region of the 5′ flanking region of Ha‐ ras in mice as compared to humans. These differences in DNA methylation and sequence may, in part, provide a basis for the frequent involvement of Ha‐ ras in mouse liver tumors and its virtual lack of involvement in human tumors. Int. J. Cancer 72:491–497, 1997. © 1997 Wiley‐Liss, Inc.