Abstract
The ethionine-induced genic derepression mechanism is visualized as a secondary process that occurs after the S-adenosyl-L methionine pool concentrations are lowered to critical levels. Although DNA methylation has been shown to be correlated with genic activity, the times observed for inducement (3 days) of the alpha-fetoprotein gene and its reversibility (within 7 days) does not make it likely that alterations in the methylated status of DNA is involved. The specific mechanism is theorized to be as follows: the adenine moiety of S-adenosyl-L-methionine base-pairs with thymine of a specific structural area of the alpha-fetoprotein gene. The process is visualized as a frequent event during moments of structural relaxation of an otherwise hyperspiralized condition of the chromatin. This weak hydrogen bonding situation allows the methylation by protein methylases of a precursor chromatin protein that after methylation by the S-adenosyl-L methionine which is base-paired to the specific DNA site, conformationally is set or locked into place and acts as a specific repressor for the alpha-fetoprotein gene. This subsequently disallows RNA polymerase activity of the region. During turnover of this chromatin protein the replacement of the methylated repressor is normally maintained. But if the S-adenosyl-L-methionine pool concentration is lowered to a level below that required for base-pairing by the adenine moiety, then the repressed conformational condition of the alpha-fetoprotein gene is altered allowing transcription. In this manner the correlation between low S-adenosyl-L-methionine and alpha-fetoprotein synthesis can be made.
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