Role of TIF1α as a modulator of embryonic transcription in the mouse zygote

The first events of the development of any embryo are under maternal control until the zygotic genome becomes activated. In the mouse embryo, the major wave of transcription activation occurs at the 2-cell stage, but transcription starts already at the zygote (1-cell) stage. Very little is known about the molecules involved in this process. We show that the transcription intermediary factor 1 alpha (TIF1alpha) is involved in modulating gene expression during the first wave of transcription activation. At the onset of genome activation, TIF1alpha translocates from the cytoplasm into the pronuclei to sites of active transcription. These sites are enriched with the chromatin remodelers BRG-1 and SNF2H. When we ablate TIF1alpha through either RNA interference (RNAi) or microinjection of specific antibodies into zygotes, most of the embryos arrest their development at the 2-4-cell stage transition. The ablation of TIF1alpha leads to mislocalization of RNA polymerase II and the chromatin remodelers SNF2H and BRG-1. Using a chromatin immunoprecipitation cloning approach, we identify genes that are regulated by TIF1alpha in the zygote and find that transcription of these genes is misregulated upon TIF1alpha ablation. We further show that the expression of some of these genes is dependent on SNF2H and that RNAi for SNF2H compromises development, suggesting that TIF1alpha mediates activation of gene expression in the zygote via SNF2H. These studies indicate that TIF1alpha is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo.