The developmental activation of the chicken lysozyme locus in transgenic mice requires the interaction of a subset of enhancer elements with the promoter.
The developmental activation of the chicken lysozyme locus in transgenic mice requires the interaction of a subset of enhancer elements with the promoter.
复制标题
DOI：
10.1093/nar/25.15.2992
复制
发表时间：
1997-08
影响因子：
14.9
通讯作者：
M. C. Huber;U. Jägle;G. Krüger;C. Bonifer
中科院分区：
文献类型：
--
作者：
M. C. Huber;U. Jägle;G. Krüger;C. Bonifer
完整的鸡溶菌酶基因在转基因小鼠巨噬细胞中以位置无关的方式表达，并形成与鸡细胞内源基因相同的染色质结构。个别溶菌酶顺式调控元件在不同发育阶段重组其染色质结构。因此，它们的活动是发育调节的，表明这些元件在基因座激活中的不同作用。我们以前已经证明，在正确的发育阶段，一组增强子元件和启动子足以激活鸡溶菌酶基因的转录。在这里，我们分析了鸡溶菌酶基因5‘-区顺式调控元件的染色质重组能力与启动子元件的关系，并检测了溶菌酶基因座是否携带显性染色质重组元件。为此，我们培育了携带溶菌酶启动子缺失载体的转基因小鼠品系。转基因在巨噬细胞中的表达被取消，但顺式调节元件的染色质重组能力受到不同程度的损害。一些顺式元件需要与启动子相互作用来稳定可在染色质中检测到的DNase I超敏感部位的转录因子复合体，而另一些元件则自主地重组其染色质结构。
The complete chicken lysozyme locus is expressed in a position independent fashion in macrophages of transgenic mice and forms the identical chromatin structure as observed with the endogenous gene in chicken cells. Individual lysozyme cis -regulatory elements reorganize their chromatin structure at different developmental stages. Accordingly, their activities are developmentally regulated, indicating a differential role of these elements in locus activation. We have shown previously that a subset of enhancer elements and the promoter are sufficient to activate transcription of the chicken lysozyme gene at the correct developmental stage. Here, we analyzed to which grade the developmentally controlled chromatin reorganizing capacity of cis -regulatory elements in the 5'-region of the chicken lysozyme locus is dependent on promoter elements, and we examined whether the lysozyme locus carries a dominant chromatin reorganizing element. To this end we generated transgenic mouse lines carrying constructs with a deletion of the lysozyme promoter. Expression of the transgene in macrophages is abolished, however, the chromatin reorganizing ability of the cis -regulatory elements is differentially impaired. Some cis -elements require the interaction with the promoter to stabilize transcription factor complexes detectable as DNase I hypersensitive sites in chromatin, whereas other elements reorganize their chromatin structure autonomously.