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.