We have previously shown that the autocrine embryotropin, Paf, activates members of the CREB family of transcription factors at the time of embryonic genome activation. These transcription factors act on the CRE response element of the genome, which is present in over 4000 potential target genes. Included in these targets are many genes that encode other transcription factors. In this study we examined the response of a range of transcription factor genes to exogenous Paf challenge. We show that the mouse 2-cell embryo responds with a typical pattern of transient immediate early response gene (IEG) expression. This is followed by a secondary wave of late response gene expression. The IEG response was not dependent upon the synthesis of new proteins, and included the expression of cFos, cJun, Junb, Jund, Egr1, Fosl2, Sp4 and Cebpb. All of these transcription factor genes were induced within 20 - 40 min of Paf exposure and are known to be CRE-responsive. The productsof cFos and cJun can dimerize to form the active AP1 transcription factor. We show that a range of AP1-responsive genes (cMyc, Klf4, Stat6, Smad3, Nanog and Nfatc1) were also induced by Paf but showed increased but delayed expression (60 - 120 min) and was dependent upon protein synthesis. Further analysis showed that Paf treatment increased cellular accumulation of immuno-detectable c-MYC and NANOG in the two-cell embryo. Together with earlier studies that showed Paf caused the activation (by phosphorylation) of pre-existing CREB and ATF1 transcription factors, these results implicate cell stimulation by autocrine ligands at the time of embryonic genome activation as a mechanism for generating a diverse new transcriptome within the embryo at the time of embryo genome activation. This occurs via canonical immediate and late gene expression responses that are characteristic of trophic stimulation of somatic cells.