Reprogramming of gene expression during preimplantation development

✍ Scribed by Schultz, Richard M.; Davis, Warren; Stein, Paula; Svoboda, Petr

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 127 KB
• Volume: 285
• Category: Article
• ISSN: 0022-104X
• DOI: 10.1002/(sici)1097-010x(19991015)285:3<276::aid-jez11>3.0.co;2-k

✦ Synopsis

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.