Regulation of zygotic gene activation in the preimplantation mouse embryo:Global activation and repression of gene expression

Superimposed on the activation of the embryonic genome in the preimplantati on mouse embryo is the formation of a transcriptionally repressive state du ring the two-cell stage. This repression appears mediated at the level of c hromatin structure, because it is reversed by inducing histone hyperacetyla tion or inhibiting the second round of DNA replication. We report that of m ore than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repressi on is scored as either a decrease in amplicon expression that occurs betwee n the two-cell and four-cell stages or on the ability of either trichostati n A tan inhibitor of histone deacetylases) or aphidicolin tan inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyze d likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone h yperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relativel y promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatibl e with further development.