Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets.

CD177 presents antigens in allo- and autoimmune diseases on the neutrophil surface. Individuals can be either CD177-deficient or harbor distinct CD177 and CD177 neutrophil subsets. We studied mechanisms controlling subset-restricted CD177 expression in bimodal individuals. CD177, but not CD177 neutrophils, produced CD177 protein and mRNA. Haplotype analysis indicated a unique monoallelic expression pattern, where the offspring stably transcribed either the maternal or paternal allele. Hematopoietic stem cells expressed both alleles and silenced one copy during neutrophil differentiation. ChIP and reporter assays in HeLa cells with monoallelic expression showed that methylation reduced reporter activity, whereas demethylation caused biallelic expression. HeLa cell transfection with c-Jun and c-Fos increased mRNA. Importantly, CD177 human neutrophils, but not CD177 neutrophils, showed a euchromatic promoter, unmethylated CpGs, and c-Jun and c-Fos binding. We describe epigenetic mechanisms explaining the two distinct CD177 neutrophil subsets and a novel monoallelic expression pattern that does not follow classical random monoallelic expression or imprinting.