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

II4 and II13, closely linked genes, are expressed monoallelically in TH2 cells. Four different approaches (RNA FISH, cultures from II13T-II4/II13-G4 mice, cultures from heterozygous II13-II4 double knockout mice, and a highly selected set of BABL/c*CAST/Ei clones displaying strong II4 allelic bias) were utilized to study monoallelic expression of II4 and coexpression of II4 and II13 on the same chromosome. There was a random probability for expression of one or two II4 and one or two II13 alleles; coexpression of cis and trans II4 and II13 alleles was equally probable. Histone H3 acetylation of CNS1, located in the II13-II4 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 II4 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 II4 and II13 alleles.