Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13.
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.
Guo
Liying
L
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. lguo@niaid.nih.gov
Hu-Li
Jane
J
Paul
William E
WE
D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic
D006657:Histones; D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4