Early genome remodeling is a black box that somehow helps reset the genome for development. In mice, the zygotic genome is activated early, with a small wave of transcription starting in the one-cell zygote and a much larger wave appearing at the two-cell stage. On page 329, Torres-Padilla and Zernicka-Goetz report that TIF1α helps regulate the initial wave of transcription by controlling genome remodeling.

After fertilization, TIF1α translocated from the cytoplasm to both pronuclei of the one-cell stage embryo, where it localized to discrete regions of the chromatin. TIF1α colocalized with chromatin-remodeling proteins SNF2H and BRG-1 at a subset of active transcription sites.

Blocking TIF1α with RNAi or antibody injection caused mislocalization of the chromatin remodeling proteins and RNA polymerase II, suggesting that TIF1α recruits the proteins to these specific sites in the genome. Many of the treated embryos stopped developing at the two-to-four-cell stage.

Finally, using a modified ChIP procedure, the team found that TIF1α was required for the proper regulation of a specific set of genes. Closer inspection of 10 of the genes indicated that TIF1α increased the transcription of some genes, while decreasing transcription of others. SNF2H RNAi treatment disrupted transcription of some of these genes as well.

The team is currently looking to see how TIF1α leads to chromatin remodeling at this early stage of embryo development. Learning how this first wave of genome activation comes about may be important for understanding what is required for successful genome reprogramming in nuclear transfer experiments.