Lack of enhancer function in mammals is unique to oocytes and fertilized eggs

Previous studies have shown that the lack of novel coactivator activity in mouse oocytes and one-cell embryos (fertilized eggs) renders them incapable of utilizing Gal4:VP16-dependent enhancers (distal elements) but not promo ters (proximal elements) in regulating transcription. This coactivator acti vity first appears in two- to four-cell embryos coincident with the major a ctivation of zygotic gene expression. Here we show that whereas oocytes and fertilized eggs could utilize Spl-dependent promoters, they could not util ize Spl-dependent enhancers, although they showed promoter repression, whic h is a requirement for delineating enhancer function. In contrast, both Spl -dependent promoters and enhancers were functional in two- to four-cell emb ryos. Furthermore, the same embryonic stem cell mRNA that provided the coac tivator activity for Gal4: VP16-dependent enhancer function also provided S p1-dependent enhancer function in oocytes, Therefore, the coactivator activ ity appears to be a requirement for general enhancer function. To determine whether the absence of enhancer function is a unique property of oocytes o r a general property of other terminally differentiated cells, transcriptio n was examined in terminally differentiated hNT neurons and their precursor s, undifferentiated NT2 stem cells. The results showed that both cell types could utilize enhancers and promoters. Thus, in mammals, the lack of enhan cer function appears to be unique to oocytes and fertilized eggs, suggestin g that it provides a safeguard against premature activation of genes prior to zygotic gene expression during development.