GENOME ACTIVATION IN PREIMPLANTATION MAMMALIAN EMBRYOS

Temple University, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from the Investigator's Abstract): The first major task of the mammalian embryo is to transform the information provided from independent parental genomes, into a single totipotent genome able to direct the formation of a new individual. Transcriptional initiation is required to sustain embryonic metabolism before depletion of maternal mRNA and protein. Nuclear reprogramming and early genome activation (EGA) must be coordinated to avoid inappropriate gene expression while providing appropriate gene expression. If both requirements are not met, the embryo may develop abnormally or die. Due to the lack of transcription at the start of development, both nuclear reprogramming and EGA must be mediated by post-transcriptional mechanisms. It is hypothesized that this is accomplished by cytoplasmic factors through two forms of regulation. One is the post-translational modification, e.g., phosphorylation, of maternally-inherited transcription factors. A second is the translational control of maternal mRNA expression. These hypotheses will be tested: 1) nuclear transplantation experiments to determine if cytoplasmic factors of early embryos can repress or activate transcription; 2) examination of the recruitment of mRNA encoding widely used transcription factors into polysomes as an index of translational control; and 3) identification of mRNA encoding additional transcription factors that are recruited into polysomes during EGA. These studies should provide fundamental insights into the role of maternal mRNA in EGA and early development.