Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha-fetoprotein gene is conceived as being methylated in the zygote and according to the model is in a heterochromatic state and is therefore in a non-functional condition. Specific DNA methylase genes would produce methylases capable of alkylating enhancer regions of alpha-fetoprotein and certain proteins that would alter the heterochromatin condition. Also involved is a gene for the synthesis of a conformational-inducer protein that is proposed to be capable of blocking genic regions from reheterochromatizing. One of the pivotal events is the accumulation of S-adenosyl-L-methionine that reaches intracellular pool concentrations allowing other redundant active S-adenosyltransferase genes to become active. During embryogenesis specific conformational-inducer proteins would block genes such as the gene for albumin from reheterochromatizing while alpha-fetoprotein gene becomes heterochromatized during subsequent cell cycles. This heterochromatin is formed with embryonic type proteins sensitive to ribosylation-induced conformational changes. The increase in synthesis of alpha-fetoprotein followed by a decrease as albumin synthesis increases during embryogenesis is predicted by the scheme.
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PMID:Derivation of a basic mechanism of control for embryonic genes as a specific subset. 128 99

A specific mechanism was given for ethionine-induced alpha-fetoprotein gene activity and is as follows: 1. Ethionine acts on competent cell types (e.g. stem cells) having one alpha-fetoprotein-enhancer-albumin gene region that is active and possesses embryonic-like low levels of S-adenosyl-L-methionine synthesis: DNA methylase genes for the enhancer regions are in the heterochromatic state. 2. ATP: L-methionine-S-adenosyltransferase acts upon ethionine and ATP to form S-adenosyl-L-ethionine; this lowers the amount of S-adenosyl-L-methionine synthesized and in turn also the synthesis of methyl-nicotinamide; the concentration of nicotinamide increases; there is an inhibition of polyADP ribosylation; hyporibosylation of histone 1 of nucleosomes; deblocking of embryonic type heterochromatin; and finally the second alpha-fetoprotein gene becomes activated. 3. Reversal occurs with the introduction of methionine; increase of S-adenosyl-L-methionine synthesis; increased methylnicotinamide synthesis; increased polyADP-ribose synthesis; ribosylation of H-1 protein to normal levels; and then the packing configuration of chromatin causes rerepression of alpha-fetoprotein genes. It is suggested that ethionine has the ability to perturb a methyl-sensitive heterochromatin that is peculiar to chromatin synthesized during embryogenesis. Therefore such repressed embryonic genes as alpha-fetoprotein are differentially susceptible to low concentrations of active methyl groups. Ethionine causes this hypomethylated heterochromatin by interference with S-adenosyl-L-methionine synthesis.
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PMID:A specific mechanism for ethionine-induced embryonic gene activity. 768 49