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

Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13
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DOI:
10.1016/j.immuni.2005.05.008
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发表时间:
2005-07-01
期刊:
影响因子:
32.4
通讯作者:
Paul, WE
Paul, WE
中科院分区:
医学1区
文献类型:
--
作者:
Guo, LY;Hu-Li, J;Paul, WE

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II 4和II 13是紧密连锁的基因,在TH 2细胞中单等位表达。利用四种不同的方法(RNA FISH、来自II 13 T-II 4/II 13-G4小鼠的培养物、来自杂合II 13-II 4双敲除小鼠的培养物以及显示强II 4等位基因偏好的高度选择的一组BABL/c*CAST/Ei克隆)来研究II 4的单等位基因表达以及II 4和II 13在同一染色体上的共表达。有一个随机的概率表达一个或两个II 4和一个或两个II 13等位基因的顺式和反式II 4和II 13等位基因的共表达是同样可能的。位于II 13-II 4基因间区的CNS 1的组蛋白H3乙酰化允许IL-4和IL-13的表达,但不能决定其表达的程度。因此,在II 4位点的单等位性是一个复杂的过程;表达与开放的CNS 1有关,但表达的概率在其他位点受到控制。基于这些概率,单个细胞随机表达II 4和II 13等位基因。
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.