Inhibition of maize histone deacetylases by HC toxin, the host-selective toxin of Cochliobolus carbonum.
HC toxin, the host-selective toxin of the maize pathogen Cochliobolus carbonum, inhibited maize histone deacetylase (HD) at 2 microM. Chlamydocin, a related cyclic tetrapeptide, also inhibited HD activity. The toxins did not affect histone acetyltransferases. After partial purification of histone deacetylases HD1-A, HD1-B, and HD2 from germinating maize embryos, we demonstrated that the different enzymes were similarly inhibited by the toxins. Inhibitory activities were reversibly eliminated by treating toxins with 2-mercaptoethanol, presumably by modifying the carbonyl group of the epoxide-containing amino acid Aeo (2-amino-9,10-epoxy-8-oxodecanoic acid). Kinetic studies revealed that inhibition of HD was of the uncompetitive type and reversible. HC toxin, in which the epoxide group had been hydrolyzed, completely lost its inhibitory activity; when the carbonyl group of Aeo had been reduced to the corresponding alcohol, the modified toxin was less active than native toxin. In vivo treatment of embryos with HC toxin caused the accumulation of highly acetylated histone H4 subspecies and elevated acetate incorporation into H4 in susceptible-genotype embryos but not in the resistant genotype. HDs from chicken and the myxomycete Physarum polycephalum were also inhibited, indicating that the host selectivity of HC toxin is not determined by its inhibitory effect on HD. Consistent with these results, we propose a model in which HC toxin promotes the establishment of pathogenic compatibility between C. carbonum and maize by interfering with reversible histone acetylation, which is implicated in the control of fundamental cellular processes, such as chromatin structure, cell cycle progression, and gene expression.
Department of Microbiology, University of Innsbruck Medical School, Austria.
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Brosch
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Ransom
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Lechner
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Walton
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Loidl
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002645:Chickens; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D006375:Helminthosporium; D051548:Histone Acetyltransferases; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000097:blood / Q000302:isolation & purification; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010804:Physarum / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D003313:Zea mays / Q000201:enzymology*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D010456:Peptides, Cyclic; D029701:Saccharomyces cerevisiae Proteins; C006963:chlamydocin; C037654:HC toxin; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases