EVOLUTION OF GENE-REGULATION AS REVEALED BY DIFFERENTIAL REGULATION OF THE CHICKEN LYSOZYME TRANSGENE AND THE ENDOGENOUS MOUSE LYSOZYME GENE IN MOUSE MACROPHAGES
EVOLUTION OF GENE-REGULATION AS REVEALED BY DIFFERENTIAL REGULATION OF THE CHICKEN LYSOZYME TRANSGENE AND THE ENDOGENOUS MOUSE LYSOZYME GENE IN MOUSE MACROPHAGES
复制标题
DOI：
10.1111/j.1432-1033.1994.tb20045.x
复制
发表时间：
1994-11-15
期刊：
影响因子：
--
通讯作者：
SIPPEL, AE
中科院分区：
文献类型：
--
作者：
BONIFER, C;BOSCH, FX;SIPPEL, AE
溶菌酶基因表达是脊椎动物巨噬细胞分化的标志。我们之前已经证明，转基因小鼠巨噬细胞中完整鸡溶菌酶基因结构域的表达与整合转基因的拷贝数直接相关。因此，鸡在小鼠中的溶菌酶位点作为一个独立的调控单元，而不管它在宿主基因组中的随机位置。这一发现允许对同一动物内源性小鼠溶菌酶M基因和鸡溶菌酶转基因的调控进行比较分析。我们通过组织总RNA转录分析和原位杂交证明，这两个基因都在巨噬细胞中表达。在同一动物的巨噬细胞中，这两个基因对外界信号的调节有明显不同：溶菌酶转基因对影响巨噬细胞活化的各种药物有应答，而小鼠溶菌酶RNA水平在这些条件下保持不变。因此，与鸡的巨噬细胞一样，鸡的溶菌酶在小鼠巨噬细胞中的表达水平与巨噬细胞的激活状态是耦合的，而小鼠的溶菌酶则不是。我们的研究结果表明，溶菌酶基因的顺式调控元件比参与巨噬细胞特异性基因激活调控的反式作用因子的功能和表达进化得更快。
Lysozyme gene expression is a marker for macrophage differentiation in vertebrates. We have previously shown that expression of the complete chicken lysozyme gene domain in macrophages of transgenic mice is directly correlated to the copy number of integrated transgenes. Thus, the chicken lysozyme locus in the mouse acts as an independent regulatory unit irrespective of its random position in the host genome. This finding allowed a comparative analysis of the regulation of the endogenous mouse lysozyme M gene and the chicken lysozyme transgene in the same animal. We demonstrate by transcript analysis of total tissue RNA and by in situ hybridization, that both genes are expressed in macrophages. In macrophages of the same animal the regulation of both genes in response to external signals was distinctly different: the lysozyme transgene responded to various agents influencing macrophage activation, in contrast, mouse lysozyme RNA levels remained unchanged under these conditions. Thus, as in chicken macrophages, the chicken lysozyme expression level in mouse macrophages is coupled to the macrophage activation status, while the mouse lysozyme is not. Our results suggest, that the cis-regulatory elements of lysozyme genes have evolved more rapidly than the function and expression of the trans-acting factors involved in the regulation of macrophage-specific gene activation.