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Immunity. 2005 Jul;23(1):89-99.

Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13.

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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.


Il4 and Il13, closely linked genes, are expressed monoallelically in TH2 cells. Four different approaches (RNA FISH, cultures from Il13T-Il4/Il13-G4 mice, cultures from heterozygous Il13-Il4 double knockout mice, and a highly selected set of BABL/c*CAST/Ei clones displaying strong Il4 allelic bias) were utilized to study monoallelic expression of Il4 and coexpression of Il4 and Il13 on the same chromosome. There was a random probability for expression of one or two Il4 and one or two Il13 alleles; coexpression of cis and trans Il4 and Il13 alleles was equally probable. Histone H3 acetylation of CNS1, located in the Il13-Il4 intergenic region, was permissive for expression of IL-4 and IL-13 but did not determine the degree of their expression. Thus, monoallelism at the Il4 locus is a complex process; expression is linked to opening CNS1 but probability of expression is controlled at other sites. Based on these probabilities, individual cells randomly express Il4 and Il13 alleles.

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