Reprogramming of gene expression during preimplantation development

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Abstract
A fundamental problem in early mammalian development is the transformation of the highly differentiated oocyte into the totipotent blastomeres by the 2‐cell stage. This remarkable transformation probably entails reprogramming the pattern of gene expression. The maternal‐to‐zygotic transition occurs during the 1‐cell stage, i.e., 1‐cell embryo is transcriptionally active. DNA replication is a likely locus of regulation, since DNA replication, with consequent nucleosome displacement, would serve to facilitate the access of maternally derived transcription factors to their cis‐acting DNA‐binding sequences. In fact, the first round of DNA replication is essential for the expression of two genes, eIF‐1A and the transcription‐requiring complex (TRC), as well as global transcription. A growing body of evidence suggests that a transcriptionally repressive state develops during the 2‐cell stage. Interestingly, inhibiting the second round of DNA replication inhibits the decrease in expression of both the TRC and eIF‐1A, as well as total endogenous gene expression. This repression may be linked to a change in chromatin structure, since treatment of 2‐cell embryos with histone deacetylase inhibitors prevents the decrease in expression of the TRC and eIF‐1A, and also inhibits the development of the transcriptionally repressive state for global gene expression. The findings that histone deacetylases can be targeted to chromatin provide a mechanism to link histone deacetylation with repression of gene expression. J. Exp. Zool. (Mol. Dev. Evol.) 285:276–282, 1999.