Thompson E M, Renard J P
Unité de Biologie du Développement, Institut National de la Recherche Agronomique, F-78352 Jouy-en-Josas, France.
Chromosoma. 1998 Nov;107(5):321-9. doi: 10.1007/s004120050314.
Changes in chromatin structure play an important role in regulation of the HSP70.1 gene during mouse preimplantation development. Using in situ PCR we have now examined whether the spatial organization of an HSP70.1 luciferase transgene within the nucleus is also a factor in regulating its expression. The transgene showed a preferential localization towards the nuclear periphery throughout preimplantation development. This preferential location was independent of the level of constitutive activity of the transgene and did not change when transgene expression was induced through core histone hyperacetylation at the eight-cell stage or by heat shock in blastocysts. In contrast, at the two-cell stage, when embryos are unable to continue development after heat shock, thermal stress provoked a significant disruption of the nuclear location of the transgene. These results do not agree with a recent model of embryonic genome activation in mice which hypothesizes that directed, active movement of DNA within the nucleus is a determinant factor in establishing early patterns of gene expression. Instead, they are consistent with models proposing that chromatin segments are restricted to nuclear subregions, but that they remain free to undergo substantial Brownian motion.
染色质结构的变化在小鼠着床前发育过程中对HSP70.1基因的调控起着重要作用。我们现在使用原位PCR来检测HSP70.1荧光素酶转基因在细胞核内的空间组织是否也是调节其表达的一个因素。在整个着床前发育过程中，转基因显示出向核周边的优先定位。这种优先定位与转基因的组成型活性水平无关，并且当在八细胞期通过核心组蛋白超乙酰化或在囊胚期通过热休克诱导转基因表达时也不会改变。相反，在二细胞期，当胚胎在热休克后无法继续发育时，热应激会导致转基因的核定位发生显著破坏。这些结果与最近关于小鼠胚胎基因组激活的模型不一致，该模型假设DNA在细胞核内的定向、主动移动是建立早期基因表达模式的决定性因素。相反，它们与提出染色质片段被限制在核亚区域，但仍可自由进行大量布朗运动的模型一致。
