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The activation of the chicken lysozyme locus indevelopment is a cooperative process

机译：鸡溶菌酶基因座的活化发育是一个合作过程

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The chicken lysozyme gene is a marker for the myelomonocytic lineage of the hematopoietic system. In early experiments we demonstrated that correct activation of the chicken lysozyme locus in macrophages of transgenic mice requires the complete set of cis-regulatory elements. Different cis-elements are activated at distinct developmental stages and their chromatin structure is differentially remodelled. We have shown that the early onset of transcriptional activation of the chicken lysozyme locus is entirely dependent on enhancer elements which are structurally activated early in development (-6.1 kb and -3.9 kb early enhancers). However, the structural reorganization of the early enhancers requires the presence of promoter sequences. We concluded from these experiments that the early enhancers and the promoter cooperate in order to activate the lysozyme locus. Subsequently, we performed experiments aimed at elucidating the cis-regulatory requirements of chromatin rearrangement at the early enhancers. The -6.1 kb enhancer is well characterized at the molecular level and all transcription factors contributing to its activity in transfection studies are known. We have placed this element into a new sequence context on the lysozyme locus by deleting extended flanking regions and analyzed this construct in transgenic mice. Surprisingly, its chromatin rearrangement ability as judged from DNaseI hypersensitive site formation was impaired. We conclude from this experiment that the cooperation of enhancer core and flanking sequences is necessary for enhancer activity. We hypothesize that all sequences of a gene locus serve a purpose in the developmental control of its activation.
机译：鸡溶菌酶基因是造血系统骨髓单核细胞系的标记。在早期实验中，我们证明了转基因小鼠巨噬细胞中鸡溶菌酶基因座的正确激活需要完整的顺式调控元件。不同的顺式元件在不同的发育阶段被激活，其染色质结构被不同地重塑。我们已经表明，鸡溶菌酶基因座的转录激活的早期发作完全取决于在发育早期被结构激活的增强子元件（-6.1 kb和-3.9 kb早期增强子）。但是，早期增强子的结构重组需要存在启动子序列。从这些实验中我们得出结论，早期增强子和启动子协同作用以激活溶菌酶基因座。随后，我们进行了旨在阐明早期增强子的染色质重排的顺式调控要求的实验。 -6.1 kb增强子在分子水平上得到了很好的表征，在转染研究中所有有助于其活性的转录因子都是已知的。通过删除延伸的侧翼区域，我们将该元素置于溶菌酶基因座的新序列环境中，并在转基因小鼠中分析了该构建体。令人惊讶的是，从DNaseI超敏位点形成判断其染色质重排能力受损。从该实验中我们得出结论，增强子核心和侧翼序列的合作对于增强子活性是必要的。我们假设一个基因座的所有序列都在其激活的发育控制中发挥作用。

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