| First Author | Barbot W | Year | 2002 |
| Journal | Nucleic Acids Res | Volume | 30 |
| Issue | 11 | Pages | 2365-73 |
| PubMed ID | 12034823 | Mgi Jnum | J:77064 |
| Mgi Id | MGI:2180959 | Doi | 10.1093/nar/30.11.2365 |
| Citation | Barbot W, et al. (2002) Epigenetic regulation of an IAP retrotransposon in the aging mouse: progressive demethylation and de-silencing of the element by its repetitive induction. Nucleic Acids Res 30(11):2365-73 |
| abstractText | The recent insertion of a murine intracisternal A-particle (IAP) retrotransposon within one of the introns of a housekeeping gene, the circadian m.nocturnin gene, revealed a singular expression profile, both throughout the daytime and the mouse life span. Measurement of the levels of transcripts from this element by quantitative real-time RT-PCR, in organs of 1-24-month-old mice, disclosed that the inserted element--which is part of a large family of otherwise severely repressed mobile elements--becomes active upon aging, specifically in the liver where the m.nocturnin housekeeping gene is expressed in a circadian manner and induces a circadian expression of the IAP sequence. This age-dependent induction is cell-autonomous, as it persists in hepatocytes in primary culture. We further show, using methylation-sensitive enzymes, a correlation between the life-time kinetics of this process and a liver-specific demethylation of the IAP promoter. These results strongly support a model whereby the progressive demethylation and turning on of the IAP sequence is the sole result of the transient, daily activation-throughout the mouse life span--of its promoter. This phenomenon, which develops on a timescale of months to years in the aging mouse, might reveal a general epigenetic--and stochastic--process, which could account for a large series of events associated with cell and animal aging. |
