Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XVII. Heterochromatin mechanisms.
A mechanism for induced embryonic gene expression via a process of deheterochromatization using a model carcinogen has been derived. First ethionine becomes activated to S-adenosyl-L-ethionine which inhibits the methylation of nicotinamide, a resulting product of polyADP-ribose polymerase. This causes hyporibosylated nucleosome core histones which normally would base pair by virtue of the adenine moieties with thymidine-rich regions of DNA, being the precursor of heterochromatin. Thus in the anomalous state a deheterochromatized condition of embryonic genes would be created. Possibly embryonic genes are dispersed in AT-rich regions potentially capable of becoming hyperspiralized by this process. Repressable embryonic genes would not be inactivated. It was also noted that hyomethylated non-histone chromatin proteins cause an extension of the nucleosome chanins which would also favor the above situation. This mechanism explains our experimental findings of the relatively rapid reversal of ethionine induced alpha-fetoprotein levels by methionine. The process of heterochromatization is hypothesized to be induced by short (pentanucleotides) moities of poly (ADP-ribose), formed on core histones, that hydrogen bond to thymidine rich inter Nu body DNA.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D005001:Ethionine / Q000494:pharmacology; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D000509:alpha-Fetoproteins / Q000235:genetics
D002273:Carcinogens; D006570:Heterochromatin; D000509:alpha-Fetoproteins; D005001:Ethionine