Regulation of Gene Expression at the Beginning of Mammalian Development

Preimplantation development in the mouse involves the expression of about 11 000 genes, only a few hundred of which appear during the transition from maternal to zygotic gene expression. Transcription begins in most, if not all, mammals during the late one-cell stage (phase I), but expression of most zygotic genes is delayed until the two-cell to the 16-cell stage, depending on the species. In mice, a small group of genes are expressed immediately after the first mitosis, while a larger group of genes are expressed during the subsequent G2 phase. Zygotic gene activation (ZGA) is delayed by a time-dependent mechanism, termed the “zygotic clock,” that regulates both transcription and translation. The zygotic clock involves the post-translational modification of RNA polymerases, the translational control of maternal gene expression, the developmental acquisition of chromatin-mediated repression, and the ability to alleviate this repression with sequence-specific enhancers. The delay imposed by this “clock” allows remodeling of chromatin into a form that globally represses gene activity so that selected genes can then be activated in a temporally and spatially specific program. Some transcription factors (e.g., Sp1, TBP) function from the oocyte through to the embryo, while others (e.g., Tead2, Tead4, Oct4) are selectively expressed during ZGA. Dramatic changes also occur in DNA methylation. However, while DNA methylation is linked to X-chromosome inactivation, genomic imprinting, and the silencing of transposable elements, a direct role for DNA methylation in regulating gene expression during animal development has yet to be demonstrated. Keywords: Promoter; Enhancer; TATA-box; Preimplantation embryo; Peri-implantation