Preferential nuclear location of a transgene does not depend on its transcriptional activity during early mouse development

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 luciferas e transgene within the nucleus is also a factor in regulating its expressio n. The transgene showed a preferential localization towards the nuclear per iphery throughout preimplantation development. This preferential location w as independent of the level of constitutive activity of the transgene and d id not change when transgene expression was induced through core histone hy peracetylation at the eight-cell stage or by heat shock in blastocysts. In contrast, at the two-cell stage, when embryos are unable to continue develo pment after heat shock, thermal stress provoked a significant disruption of the nuclear location of the transgene. These results do not agree with a r ecent 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 consi stent with models proposing that chromatin segments are restricted to nucle ar subregions, but that they remain free to undergo substantial Brownian mo tion.