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 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.
Schultz
R M
RM
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018, USA. rschultz@sas.upenn.edu
Davis
W
W
Stein
P
P
Svoboda
P
P
D000818:Animals; D004261:DNA Replication / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015053:Zygote / Q000502:physiology