Translation of Maternal Messenger Ribonucleic Acids Encoding Transcription Factors During Genome Activation in Early Mouse Embryos1

Abstract

Embryonic genome activation (EGA) in mice is sensitive to treatment with cycloheximide, indicating that protein synthesis plays an important role in mediating EGA. We hypothesized that regulated maternal mRNA recruitment may control the time of EGA by controlling the time of appearance of certain transcription factors (TFs). We also hypothesized that synthesis of other TFs may contribute to EGA independently of controlling the timing of EGA. To test these hypotheses, we used sucrose density gradient fractionation coupled to a quantitative reverse transcription-polymerase chain reaction method to compare polysomal mRNA abundances of specific TF mRNAs between metaphase II oocytes, 1-cell-stage embryos, and 2-cell-stage embryos. We observed a 2-cell-stage-specific increase in polysomal abundance of mouse TEA DNA binding domain 2 (mTEAD-2) mRNA, coincident with the first appearance of mTEAD activity in the early embryo. The mRNAs encoding Sp1, TATA binding protein, and cyclic AMP response element binding protein did not undergo translational recruitment, but exhibited differences in polysomal abundance. We also observed a continuous, high proportion in the polysomal fraction for the mRNA encoding ribosomal protein L23 mRNA, which contrasted with the patterns observed for other maternal transcripts. These observations are consistent with the hypothesis that regulated recruitment of maternal TF mRNAs may control the time of activation of some genes during EGA, and that continuous synthesis of other TFs, like Sp1, may facilitate EGA.

Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development

“…The genes in this cluster (cluster 3) are characterized by over-representation of the nucleic acid and protein catabolism pathways. During this developmental window, maternal mRNAs are loaded onto polysomes (Potireddy et al, 2006), translocated and degraded, and widespread cytoplasmic catabolism of oocyte-inherited proteins is required for the correct initiation of EGA (Bushati et al, 2008;Lieberfarb et al, 1996;Wang and Latham, 2000). Moreover, the transcripts in this cluster have an over-representation of binding sites for POU transcription factors.…”

Delay of ZGA initiation occurred in 2-cell blocked mouse embryos

“…Recently, a 2-cell-stagespecific increase in polyribosomal abundance of maternal mRNA encoding some transcription factors (TFs) was observed. It was hypothesized that the regulated recruitment of maternal TFs mRNA may control the time of ZGA by controlling the time of appearance of certain TFs [28]. From this point of view, we can suppose that 2-cell block must involve delayed expression or activation of one or more transacting factors required for transcription or translation, or both of those genes that will trigger the zygotic clock [4].…”

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

“…In Xenopus, maternally encoded proteins are similarly necessary for establishment of the embryonic axis and rapid early cell divisions (reviewed in . Because the embryonic genome in mouse is transcribed at the two-cell stage, many maternal proteins are involved in activating the embryonic genome as transcription factors and chromatin remodeling factors (Wang and Latham, 2000;Potireddy et al, 2006). Other functional classes of newly translated proteins in mouse include those involved in metabolism, cell cycle regulation, and apoptosis (Potireddy et al, 2006).…”