Reprogramming of gene expression during preimplantation development

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 I-cell stage, i.e., I-cell embryo is transcriptionally active. D NA replication is a likely locus of regulation, since DNA replication, with consequent nucleosome displacement, would serve to facilitate the access o f 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 (T RC), as well as global transcription. A growing body of evidence suggests t hat 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 endogen ous gene expression. This repression may be linked to a change in chromatin structure, since treatment of 2-cell embryos with histone deacetylase inhi bitors prevents the decrease in expression of the TRC and eIF-1A, and also inhibits the development of the transcriptionally repressive state for glob al gene expression. The findings that histone deacetylases can be targeted to chromatin provide a mechanism to Link histone deacetylation with repress ion of gene expression. (C) 1999 Wiley-Liss, Inc.