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

Abstract

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 α (TIF1α) is involved in modulating gene expression during the first wave of transcription activation. At the onset of genome activation, TIF1α 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 TIF1α 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 TIF1α 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 TIF1α in the zygote and find that transcription of these genes is misregulated upon TIF1α 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 TIF1α mediates activation of gene expression in the zygote via SNF2H. These studies indicate that TIF1α is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo.

ATP-dependent chromatin remodeling during mammalian development

“…SNF2H, as well as the BAF complex component BRG1, colocalizes with and regulates the function of transcription intermediary factor 1α (TIF1α), which mediates the initial wave of transcription in the one-cell zygote before ZGA occurs. Both SNF2H and BRG1 are mislocalized in the absence of TIF1α and inhibition of Snf2h levels results in misregulation of a subset of TIF1α-regulated genes, indicating a crucial role for SNF2H in zygotic transcription regulation (Torres-Padilla and Zernicka-Goetz, 2006). Consistent with this role, SNF2H was shown to be essential for early mouse development; homozygous Snf2h mutants display peri-implantation lethality because of a failure to proliferate both trophectoderm and ICM (Stopka and Skoultchi, 2003).…”

Zygotic Gene Activation and Maternal Factors in Mammals

“…In Brg1-null females, oogenesis and ovulation occur normally, suggesting that Brg1 is the first maternal-effect gene that is directly involved in ZGA in mammals. Transcription intermediary factor 1α (TIF1α) modulates the transcription of a set of genes in mouse zygotes [85]. At the onset of ZGA, TIF1α translocates from the cytoplasm to the pronuclei.…”

T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

“…Trim24 is expressed early in the developing embryo (42) in the developing nervous system (43), liver (28,44), intestine (45), lung (46), and microglia (47). Unlike Trim28 (26) and Trim33 (48), which have reported roles in T cells, Trim24 has not been studied within the immune system.…”