SUMMARY Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle and differentiation independent manner. Here, we show that in the mouse olfactory epithelium, olfactory receptor (OR) genes are marked, in a highly dynamic fashion, with the molecular hallmarks of constitutive heterochromatin, H3K9me3 and H4K20me3. The cell-type and developmentally dependent deposition of these marks along the OR clusters is, most likely, reversed during the process of OR choice to allow for monogenic and monoallelic OR expression. In contrast to the current view of OR choice, our data suggest that OR silencing takes place before OR expression, indicating that it is not the product of an OR-elicited feedback signal. This suggests a new role for chromatin-mediated silencing as the molecular foundation upon which singular and stochastic selection can be applied.

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SUMMARY. Separate groups of mice challenged intravenously with either the blastospore or hyphal forms of the same strain of Candida albicans were examined for comparative mortality rates, organ localisation, and tissue and cellular response to the organisms. Blastospores were more rapidly and consistently fatal to mice than the hyphae. Relatively more hyphal elements than blastospores were initially localised in the lungs but more blastospores than hyphal elements were trapped in the liver. The cells of both forms were more effectively killed in the lungs than in other organs. Blastospores initially found in the kidneys increased rapidly in numbers, but hyphal inocula either grew slowly in the kidneys or were eliminated. After mice were challenged with either hyphae or blastospores the initial inflammatory response in the lungs and liver was predominantly of polymorphonuclear leukocytes, but macrophages were the first inflammatory cells to be seen in kidney sections. Peripheral blood counts showed a leukocytosis in mice of both groups although only blastospores resulted in increased numbers of circulating atypical lymphocytes. The results indicated that lungs may play a more important role than other reticuloendothelial organs in innate resistance to vascular invasion by either of the morphological forms of C. albicans, and macrophages may be crucial to host resistance to renal invasion by this fungus.

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